Endoscopic Cryoablation Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

BACKGROUND AND OBJECTIVE: Cryoablation is a traditional antitumor therapy with good prospects for development. The efficacy of endoscopic management as a kidney-sparing surgery for high-risk upper tract urothelial carcinoma (UTUC) remains controversial. Our aim was to evaluate the impact of endoscopic cryoablation (ECA) versus radical nephroureterectomy (RNU) on survival outcomes, renal function, and complications. METHODS: We retrospectively analyzed data for 116 patients with newly diagnosed high-risk UTUC who underwent either ECA (n = 13) or RNU (n = 103) from March 25, 2019 to December 8, 2021. Propensity score matching (1:4) using the nearest neighbor method was performed before analysis. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), intravesical recurrence-free survival (RFS), the change in renal function, and treatment-emergent adverse events (TEAEs). KEY FINDINGS AND LIMITATIONS: At median follow-up of 28.2 mo for the ECA group and 27.6 mo for the RNU group, 2-yr OS (82% vs 84%), PFS (73% vs 71%), and intravesical RFS (81% vs 83%) rates after matching did not significantly differ. A decline in renal function was observed after RNU, but not after ECA. Five (41.7%) patients in the ECA group reported six TEAEs, and 17 patients (35.4%) in the RNU group reported 20 TEAEs. CONCLUSIONS AND CLINICAL IMPLICATIONS: In comparison to RNU, ECA for UTUC resulted in noninferior oncological outcomes and superior preservation of renal function. PATIENT SUMMARY: Our study suggests that a treatment called endoscopic cryoablation for high-risk cancer in the upper urinary tract can help in preserving kidney function, with similar survival outcomes to those after more extensive surgery. This option can be considered for selected patients with a strong preference for kidney preservation.

Posterior endpoint determination of the lumbar pedicle central axis on the anterior-posterior fluoroscopic image for pedicle screw insertion.

The transpedicular procedure has been widely used in spinal surgery. The determination of the best entry point is the key to perform a successful transpedicular procedure. Various techniques have been used to determine this point, but the results are variable. This study was carried out to determine the posterior endpoint of the lumbar pedicle central axis on the standard anterior-posterior (AP) fluoroscopic images. Computer-aided design technology was used to determine the pedicle central axis and the posterior endpoint of the pedicle central axis on the posterior aspect of the vertebra. The standard AP fluoroscopic image of the lumbar vertebral models by three-dimensional printing was achieved. The endpoint projection on the AP fluoroscopic image was determined in reference to the pedicle cortex projection by the measurements of the angle and distance on the established X-Y coordinate system of the radiologic image. The projection of posterior endpoint of the lumbar pedicle central axis were found to be superior to the X-axis of the established X-Y coordinate system and was located on the pedicle cortex projection on the standard AP fluoroscopic image of the vertebra. The projection point was distributed in different sectors in the coordinate system. It was located superior to the X-axis by 18° to 26° at L1, while they were located superior to the X-axis by 12° to 14° at L2 to L5. The projections of posterior endpoints of the lumbar pedicle central axis were located in different positions on the standard AP fluoroscopic image of the vertebra. The determination method of the projection point was helpful for selecting an entry point for a transpedicular procedure with a fluoroscopic technique.

Combining Classic and Novel Neutrophil-Related Biomarkers to Identify Non-Small-Cell Lung Cancer.

BACKGROUND: Recent studies have revealed that neutrophils play a crucial role in cancer progression. This study aimed to explore the diagnostic value of neutrophil-related biomarkers for non-small-cell lung cancer (NSCLC). METHODS: We initially assessed the associations between classic neutrophil-related biomarkers (neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil counts (NEU), absolute lymphocyte counts (LYM)) and NSCLC in 3942 cases and 6791 controls. Then, we measured 11 novel neutrophil-related biomarkers via Luminex Assays in 132 cases and 66 controls, individually matching on sex and age (±5 years), and evaluated their associations with NSCLC risk. We also developed the predictive models by sequentially adding variables of interest and assessed model improvement. RESULTS: Interleukin-6 (IL-6) (odds ratio (OR) = 10.687, 95% confidence interval (CI): 3.875, 29.473) and Interleukin 1 Receptor Antagonist (IL-1RA) (OR = 8.113, 95% CI: 3.182, 20.689) shows strong associations with NSCLC risk after adjusting for body mass index, smoking status, NLR, and carcinoembryonic antigen. Adding the two identified biomarkers to the predictive model significantly elevated the model performance from an area under the receiver operating characteristic curve of 0.716 to 0.851 with a net reclassification improvement of 97.73%. CONCLUSIONS: IL-6 and IL-1RA were recognized as independent risk factors for NSCLC, improving the predictive performance of the model in identifying disease.

Comparing three-dimensional and two-dimensional deep-learning, radiomics, and fusion models for predicting occult lymph node metastasis in laryngeal squamous cell carcinoma based on CT imaging: a multicentre, retrospective, diagnostic study.

Background: The occult lymph node metastasis (LNM) of laryngeal squamous cell carcinoma (LSCC) affects the treatment and prognosis of patients. This study aimed to comprehensively compare the performance of the three-dimensional and two-dimensional deep learning models, radiomics model, and the fusion models for predicting occult LNM in LSCC. Methods: In this retrospective diagnostic study, a total of 553 patients with clinical N0 stage LSCC, who underwent surgical treatment without distant metastasis and multiple primary cancers, were consecutively enrolled from four Chinese medical centres between January 01, 2016 and December 30, 2020. The participant data were manually retrieved from medical records, imaging databases, and pathology reports. The study cohort was divided into a training set (n = 300), an internal test set (n = 89), and two external test sets (n = 120 and 44, respectively). The three-dimensional deep learning (3D DL), two-dimensional deep learning (2D DL), and radiomics model were developed using CT images of the primary tumor. The clinical model was constructed based on clinical and radiological features. Two fusion strategies were utilized to develop the fusion model: the feature-based DLRad_FB model and the decision-based DLRad_DB model. The discriminative ability and correlation of 3D DL, 2D DL and radiomics features were analysed comprehensively. The performances of the predictive models were evaluated based on the pathological diagnosis. Findings: The 3D DL features had superior discriminative ability and lower internal redundancy compared to 2D DL and radiomics features. The DLRad_DB model achieved the highest AUC (0.89-0.90) among all the study sets, significantly outperforming the clinical model (AUC = 0.73-0.78, P = 0.0001-0.042, Delong test). Compared to the DLRad_DB model, the AUC values for the DLRad_FB, 3D DL, 2D DL, and radiomics models were 0.82-0.84 (P = 0.025-0.46), 0.86-0.89 (P = 0.75-0.97), 0.83-0.86 (P = 0.029-0.66), and 0.79-0.82 (P = 0.0072-0.10), respectively in the study sets. Additionally, the DLRad_DB model exhibited the best sensitivity (82-88%) and specificity (79-85%) in the test sets. Interpretation: The decision-based fusion model DLRad_DB, which combines 3D DL, 2D DL, radiomics, and clinical data, can be utilized to predict occult LNM in LSCC. This has the potential to minimize unnecessary lymph node dissection and prophylactic radiotherapy in patients with cN0 disease. Funding: National Natural Science Foundation of China, Natural Science Foundation of Shandong Province.

Combining MTI-31 with RAD001 inhibits tumor growth and invasion of kidney cancer by activating autophagy.

At most of the times, patients who are diagnosed with kidney cancer should be provided with systemic treatment as drug resistance is a challenging issue in the treatment of this disease. The progression of the cancer can be inhibited with the help of mTOR inhibitors namely RAD001 (everolimus) and MTI-31. In literature, it has been revealed that these mTOR inhibitors have the potential to stimulate autophagy. This degradation pathway boosts the survival rate of the cancerous cells that are subjected to anti-cancer therapy. In this study, CCK8, colony formation assays, and ethynyl deoxyuridine (EdU) analysis were conducted to detect cell proliferation. Furthermore, Transwell assays were also conducted for cell migration analysis. In addition to these, the researchers also performed the flow cytometry process to identify the cells that are undergoing apoptosis. In vivo, experiments were conducted to measure the growth of tumors and metastasis. In this study, the treatment provided through a combination of MTI-31 and RAD001 significantly inhibited the kidney cancer cells' proliferation and tumor growth. Furthermore, there was a notable reduction in the migration and invasion of kidney cancer cells upon the neighboring cells. The outcomes from the mechanistic studies infer that the combination of MTI-31 and RAD001 increases the LC3 levels, which in turn translates into the activation of autophagy. To conclude, the combination of MTI-31 and RAD001 improves the anti-cancerous impact produced by RAD001 in vivo through the promotion of autophagy.

[Efficacy evaluation of transaxillary non-inflatable endoscopic surgery and open neck surgery in the treatment of PTC: a single center report of 342 cases].

Objective:To compare the clinical effect of transaxillary non-inflatable endoscopic surgery and traditional open thyroid surgery in the treatment of PTC. Methods:A retrospective analysis was performed on 342 patients with PTC treated in the Otorhinolaryngology Department of Qilu Hospital of Shandong University from December 2020 to December 2022. There were 73 males and 269 females, aged 16-72 years, who underwent unilateral non-inflatable transaxillary endoscopic thyroid surgery（endoscopic group） and unilateral traditional open thyroid surgery（open group）. There were 108 patients in the endoscopic group and 234 in the open group. Results:The endoscopic group was lower in age（37.1±9.4 vs 43.5±11.2） years and BMI（23.4±3.4 vs 25.7±3.8 ）kg/m² than that in the open group, and the difference was statistically significant（t was 5.53, 5.67 respectively, P<0.01）. There was no significant difference in hospitalization days between the two groups（P>0.05）. The logarithmic curve of the operation time showed a smooth downward trend, and the overall operation time of the endoscopic group was relatively consistent. There was no significant difference in intraoperative blood loss between the endoscopic group（13.3±3.2） mL and the open group（14.7±6.3） mL（P>0.05）, but the operation time（130.1±37.9） min was longer than that in the open group（57.4±13.7） min, and the difference was statistically significant（t=19.40, P<0.01）. There was no significant difference in complications such as temporary recurrent laryngeal nerve injury within 3 days after operation between the two groups（P>0.05）. The aesthetic satisfaction score of the surgical incision and the incision concealment effect score in the endoscopic group were higher than those in the open group, and the difference was statistically significant（P<0.05）. Conclusion:Compared with traditional open thyroidectomy, transaxillary non-inflatable endoscopic thyroidectomy has more advantages in the concealment and aesthetics of postoperative incision. Although the former has longer operation time and more drainage, it is still a safe and feasible surgical method with good postoperative clinical effect.

[Advances of spatial omics in the individualized diagnosis and treatment of head and neck cancer].

Spatialomics is another research hotspot of biotechnology after single-cell sequencing technology, which can make up for the defect that single-cell sequencing technology can not obtain cell spatial distribution information. Spatialomics mainly studies the relative position of cells in tissue samples to reveal the effect of cell spatial distribution on diseases. In recent years, spatialomics has made new progress in the pathogenesis, target exploration, drug development and many other aspects of head and neck tumors. This paper summarizes the latest progress of spatialomics in the diagnosis and treatment of head and neck cancer.

[A case of pediatric tracheal inflammatory myofibroblastic tumor].

Inflammatory myofibroblastic tumor is a rare tumor of mesenchymal origin. A case of intratracheal inflammatory myofibroblastic tumor in a male child was reported. The clinical characteristics, diagnosis, treatment and prognosis of the disease were reviewed based on the literature, and a differential diagnosis between inflammatory myofibroblastic tumor and hamartoma was performed to ultimately confirm the nature of the tumor in the child.

Immune-active tumor-adjacent tissues are associated with favorable prognosis in stage I lung squamous cell carcinoma.

The immunogenomic features of tumor-adjacent lungs (TALs) in stage I lung squamous cell carcinoma (LUSC) are not clear. Multiomics analyses of tumor tissues and paired TALs from 59 stage I LUSC patients were performed. Compared to tumors, TALs exhibited a better-preserved immune contexture indicated by upregulation of immune pathways, increased immune infiltration, and higher expression of immune effector molecules. Notably, TALs had no mutations in PTEN and KEAP1, a lower incidence of human leukocyte antigen (HLA) loss and higher expression of HLA class I genes, major histocompatibility complex (MHC) I chaperones, and interferon (IFN)-γ-associated genes. Digital spatial profiling validated the generally higher immune infiltration in TALs and revealed a higher level of immune heterogeneity in LUSC tumors. Importantly, patients with higher immune infiltration in TALs had significantly longer survival, while high immune heterogeneity was associated with inferior patient survival. Our work can be considered in the selection of patients for adjuvant therapy, especially immunotherapy.

Analysis of myosin genes in HNSCC and identify MYL1 as a specific poor prognostic biomarker, promotes tumor metastasis and correlates with tumor immune infiltration in HNSCC.

Head neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors which ranks the sixth incidence in the world. Although treatments for HNSCC have improved significantly in recent years, its recurrence rate and mortality rate remain high. Myosin genes have been studied in a variety of tumors, however its role in HNSCC has not been elucidated. GSE58911 and GSE30784 gene expression profile analysis were performed to detect significantly dys-regulated myosin genes in HNSCC. The Cancer Genome Atlas (TCGA) HNSCC database was used to verify the dys-regulated myosin genes and study the relationship between these genes and prognosis in HNSCC. The results showed that MYL1, MYL2, MYL3, MYH2, and MYH7 were down-regulated, while MYH10 was up-regulated in patients with HNSCC. Interestingly, MYL1, MYL2, MYH1, MYH2, and MYH7 were shown to be unfavorable prognostic markers in HNSCC. It is also worth noting that MYL1 was a specific unfavorable prognostic biomarker in HNSCC. MYL1, MYL2, MYL3, MYH2, MYH7, and MYH10 promoted CD4 + T cells activation in HNSCC. MYL1 was proved to be down-regulated in HNSCC tissues compared to normal tissues at protein levels. MYL1 overexpression had no effect on proliferation, but significantly promoted migration of Fadu cells. MYL1 increased EGF and EGFR protein expression levels. Moreover, there is a positive correlation between MYL1 expression and Tcm CD8 cells, Tcm CD4 + cells, NK cells, Mast cells, NKT cells, Tfh cells and Treg cells in HNSCC. Overall, MYL1 facilitates tumor metastasis and correlates with tumor immune infiltration in HNSCC and these effects may be associated with the EGF/EGFR pathway.

Global burden of esophageal cancer attributable to smoking: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Epidemiological trends of esophageal cancer attributable to smoking remain unclear. This study aimed to estimate the spatiotemporal trends of the esophageal cancer burden attributable to smoking to assist in global esophageal cancer prevention and smoking cessation. Methods: Data on esophageal cancer attributable to smoking were obtained from the Global Burden of Disease Study 2019. The number and age-standardized rates of esophageal cancer mortality (ASMR) and disability-adjusted life years (ASDR) were analyzed by age, sex, and location. Joinpoint regression analysis was used to analyze the temporal trends of esophageal cancer burden attributable to smoking over 30 years. Results: In 2019, the number of global esophageal cancer deaths and disability-adjusted life years (DALYs) attributable to smoking was approximately 203,000 and 475 million, respectively. The global esophageal cancer deaths and DALYs due to smoking were approximately 1.5-fold increased from 1990 to 2019, but the corresponding ASMR and ASDR had decreased. The heaviest burden occurred in East Asia, Mongolia, and the middle socio-demographic index (SDI) region. The male-to-female ratio was approximately 12.7 in the esophageal cancer deaths and DALYs and was approximately 14.3 in the ASMR and ASDR. The heaviest burden appeared in the 60-74 years age group. The estimated annual percentage change (EAPC) in ASMR was highly negatively associated with ASMR in 1990 (ρ = -0.41, p < 0.001) and SDI in 2019 (ρ = -0.29, p < 0.001). Conclusion: Despite reductions in ASMR and ASDR, the esophageal cancer burden attributable to smoking remains heavy, especially in middle SDI regions. Active tobacco control can reduce esophageal cancer burden.

Single-cell RNA sequencing reveals tumor immune microenvironment in human hypopharygeal squamous cell carcinoma and lymphatic metastasis.

Background: Human hypopharygeal squamous cell carcinoma (HSCC) is a common head and neck cancer with a poor prognosis in advanced stages. The occurrence and development of tumor is the result of mutual influence and co-evolution between tumor cells and tumor microenvironment (TME). Tumor immune microenvironment (TIME) refers to the immune microenvironment surrounding tumor cells. Studying TIME in HSCC could provide new targets and therapeutic strategies for HSCC. Methods: We performed single-cell RNA sequencing (scRNA-seq) and analysis of hypopharyngeal carcinoma, paracancerous, and lymphoid tissues from five HSCC patients. Subdivide of B cells, T cells, macrophages cells, and monocytes and their distribution in three kinds of tissues as well as marker genes were analyzed. Different genes of IGHG1 plasma cells and SPP1+ macrophages between HSCC tissues, adjacent normal tissues and lymphatic tissues were analyzed. Additionally, we studied proliferating lymphocytes, T cells exhaustion, and T cell receptor (TCR) repertoire in three kinds of tissues. Results: Transcriptome profiles of 132,869 single cells were obtained and grouped into seven cell clusters, including epithelial cells, lymphocytes, mononuclear phagocytics system (MPs), fibroblasts, endothelial cells (ECs), plasmacytoid dendritic cells (pDCs), and mast cells. Tumor metastasis occurred in three lymphoid tissues. Four distinct populations were identified from lymphocytes, including B cells, plasma cells, T cells and proliferating lymphocytes. We found IGHA1 and IGHG1 specific plasma cells significantly overexpressed in HSCC tissues compared with normal hypopharygeal tissues and lymphatic tissues. Five distinct populations from MPs were identified, including macrophages, monocytes, mature dendritic cells (DCs), Type 1 conventional dendritic cells (cDC1) and Type 2 conventional dendritic cells (cDC2). SPP1+ macrophages were significantly overexpressed in HSCC tissues and lymphatic tissues compared with normal hypopharygeal tissues, which are thought to be M2-type macrophages. Exhaustion of CD8+ Teff cells occurred in HSCC tissues. At last, we verified that IgA and IgG1 protein expression levels were significantly up-regulated in HSCC tissues compared to adjacent normal tissues. Conclusion: Overall, this study revealed TIME in HSCC and lymphatic metastasis, and provided potential therapeutic targets for HSCC.

Protective Autophagy Attenuates the Cytotoxicity of MTI-31 in Renal Cancer Cells by Activating the ERK Pathway.

The mammalian target of rapamycin (mTOR) is a key regulatory molecular target to treat cancer, and MTI-31 is a potent mTOR inhibitory agent for the therapeutically target of the renal cell carcinoma (RCC). However, the therapeutic efficacy of MTI-31 is limited by multiple factors, including autophagy. MTI-31 can activate cells to generate autophagy, which may in turn indirectly affect cell proliferation and apoptosis. We aimed to observe changes in cell protective autophagy via the ERK pathway and explore the potential mechanism underlying drug resistance of RCC cells to MTI-31. Different concentrations of 786-O and RCC4 cells were co-cultured with MTI-31 for distinct durations. The result of autophagy marker detection by Western blot showed that MTI-31 could induce RCC cells to produce autophagy in a dose and time-dependent manner. After treating the RCC cells with the autophagy inhibitor chloroquine (CQ), CCK8 and Western blot assays demonstrated that CQ could effectively enhance cell apoptosis induced by MTI-31 and that the autophagy induced by MTI-31 was cytoprotective. In addition, CCK8 and Western blot demonstrated that MTI-31 exerted its effect by activating the ERK pathway rather than the JNK or p38 pathway. The use of the ERK inhibitor AZD6244 to block the ERK pathway could effectively promote cell apoptosis induced by MTI-31. AZD6244 attenuated the autophagy induced by MTI-31 and increased the cytotoxicity of MTI-31. Western blot also demonstrated that MTI-31-induced autophagy was mediated by the downstream regulators of ERK pathways, including Beclin-1 and Bcl-2. It demonstrated that the MTI-31 mediated activation ERK pathway is associated with the induction of autophagy, and autophagy can attenuate the cytotoxicity of MTI-31 on RCC cells. In summary, inhibition of ERK pathway-mediated autophagy can rectify drug resistance to MTI-31 effectively.