Associations between metabolic dysfunction-associated fatty liver disease, chronic kidney disease, and abdominal obesity: a national retrospective cohort study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and chronic kidney disease (CKD) present notable health challenges, however, abdominal obesity has received scant attention despite its potential role in exacerbating these conditions. Thus, we conducted a retrospective cohort study using the National Health and Nutrition Examination Surveys III (NHANES III) of the United States from 1988 to 1994 including 9161 participants, and mortality follow-up survey in 2019. Statistical analyze including univariable and multivariable Logistic and Cox regression models, and Mediation effect analyze were applied in study after adjustment for covariates. Our findings revealed that individuals with both abdominal obesity and MAFLD were more likely to be female, older and exhibit higher prevalence of advanced liver fibrosis (7.421% vs. 2.363%, p < 0.001), type 2 diabetes mellitus (T2DM) (21.484% vs. 8.318%, p < 0.001) and CKD(30.306% vs. 16.068%, p < 0.001) compared to those with MAFLD alone. MAFLD (adjusted OR: 1.392, 95% CI 1.013-1.913, p = 0.041), abdominal obesity (adjusted OR 1.456, 95% CI 1.127-1.880, p = 0.004), abdominal obesity with MAFLD (adjusted OR 1.839, 95% CI 1.377-2.456, p < 0.001), advanced fibrosis(adjusted OR 1.756, 95% CI 1.178-2.619, p = 0.006) and T2DM (adjusted OR 2.365, 95% CI 1.758-3.183, p < 0.001) were independent risk factors of CKD. The abdominal obese MAFLD group had the highest all-cause mortality as well as mortality categorized by disease during the 30-year follow-up period. Indices for measuring abdominal obesity, such as waist circumference (WC), waist-hip ratio (WHR), and lipid accumulation product (LAP), elucidated a greater mediation effect of MAFLD on CKD compared to BMI on CKD (proportion mediation 65.23%,70.68%, 71.98%, respectively vs. 32.63%). In conclusion, the coexistence of abdominal obesity and MAFLD increases the prevalence and mortality of CKD, and abdominal obesity serves as a mediator in the association between MAFLD and CKD.

Continuous cold rubidium atomic beam with enhanced flux and tunable velocity.

We present a cold atomic beam source based on a two-dimensional (2D)+ magneto-optical trap (MOT), capable of generating a continuous cold beam of 87Rb atoms with a flux up to 4.3 × 109 s-1, a mean velocity of 10.96(2.20) m/s, and a transverse temperature of 16.90(1.56) µK. Investigating the influence of high cooling laser intensity, we observe a significant population loss of atoms to hyperfine-level dark states. To account for this, we employ a multiple hyperfine level model to calculate the cooling efficiency associated with the population in dark states, subsequently modifying the scattering force. Simulations of beam flux at different cooling and repumping laser intensities using the modified scattering force are in agreement with experimental results. Optimizing repumping and cooling intensities enhances the flux by 50%. The influence of phase modulation on both the pushing and cooling lasers is experimentally studied, revealing that the mean velocity of cold atoms can be tuned from 9.5 m/s to 14.6 m/s with a phase-modulated pushing laser. The versatility of this continuous beam source, featuring high flux, controlled velocity, and narrow transverse temperature, renders it valuable for applications in atom interferometers and clocks, ultimately enhancing bandwidth, sensitivity, and signal contrast in these devices.

Quantitative Analysis of Nanoplastics in Single Cells by Subcellular Chromatography.

The accumulation and spatial distribution of intracellular nanoplastic particles provide useful information about their spatiotemporal toxicological effects mediated by the physicochemical parameters of nanoplastics in living cells. In this study, a sample injection-transfer method was designed with an accuracy of up to femtoliters to attoliters to match the volume required for ultranarrow-bore open-tubular liquid chromatography. The separation and concentration quantification of mixed polystyrenes in different regions in living cells were achieved by directly transferring picoliter/femtoliter volumes of intracellular cytoplasm to an ultranarrow-bore open-tubular chromatographic column. The measurement of pollutant concentration in different areas of a small-volume target (single cell) was realized. This method is expected to be used in the qualitative and quantitative analyses of complex, mixed, and label-free nanoplastics (a few nm in size) in the subregions of living cells.

A macropinocytosis-related gene signature predicts the prognosis and immune microenvironment in hepatocellular carcinoma.

Background: Available treatments for hepatocellular carcinoma (HCC), a common human malignancy with a low survival rate, remain unsatisfactory. Macropinocytosis (MPC), a type of endocytosis that involves the non-specific uptake of dissolved molecules, has been shown to contribute to HCC pathology; however, its biological mechanism remains unknown. Methods: The current study identified 27 macropinocytosis-related genes (MRGs) from 71 candidate genes using bioinformatics. The R software was used to create a prognostic signature model by filtering standardized mRNA expression data from HCC patients and using various methods to verify the reliability of the model and indicate immune activity. Results: The prognostic signature was constructed using seven MPC-related differentially expressed genes, GSK3B, AXIN1, RAC1, KEAP1, EHD1, GRB2, and SNX5, through LASSO Cox regression. The risk score was acquired from the expression of these genes and their corresponding coefficients. HCC patients in the discovery and validation cohorts were stratified, and the survival of low-risk score patients was improved in both cohorts. Time-dependent ROC analysis indicated that the model's prediction reliability was the highest in the short term. Subsequent immunologic analysis, including KEGG, located the immune action pathway of the differentially expressed genes in the direction of the cancer pathway, etc. Immune infiltration and immune checkpoint tests provided valuable guidance for future follow-up experiments. Conclusion: A risk model with MRGs was constructed to effectively predict HCC patient prognoses and suggest changes in the immune microenvironment during the disease process. The findings should benefit the development of a prognostic stratification and treatment strategy for HCC.

Single-Cell Metabolomics-Based Strategy for Studying the Mechanisms of Drug Action.

Studying the mechanisms of drug antitumor activity at the single-cell level can provide information about the responses of cell subpopulations to drug therapy, which is essential for the accurate treatment of cancer. Due to the small size of single cells and the low contents of metabolites, metabolomics-based approaches to studying the mechanisms of drug action at the single-cell level are lacking. Herein, we develop a label-free platform for studying the mechanisms of drug action based on single-cell metabolomics (sMDA-scM) by integrating intact living-cell electro-launching ionization mass spectrometry (ILCEI-MS) with metabolomics analysis. Using this platform, we reveal that non-small-cell lung cancer (NSCLC) cells treated by gefitinib can be clustered into two cell subpopulations with different metabolic responses. The glutathione metabolic pathway of the subpopulation containing 14.4% of the cells is not significantly affected by gefitinib, exhibiting certain resistance characteristics. The presence of these cells masked the judgment of whether cysteine and methionine metabolic pathway was remarkably influenced in the analysis of overall average results, revealing the heterogeneity of the response of single NSCLC cells to gefitinib treatment. The findings provide a basis for evaluating the early therapeutic effects of clinical medicines and insights for overcoming drug resistance in NSCLC subpopulations.

Intact living-cell electrolaunching ionization mass spectrometry for single-cell metabolomics.

While single-cell mass spectrometry can reveal cellular heterogeneity and the molecular mechanisms of intracellular biochemical reactions, its application is limited by the insufficient detection sensitivity resulting from matrix interference and sample dilution. Herein, we propose an intact living-cell electrolaunching ionization mass spectrometry (ILCEI-MS) method. A capillary emitter with a narrow-bore, constant-inner-diameter ensures that the entire living cell enters the MS ion-transfer tube. Inlet ionization improves sample utilization, and no solvent is required, preventing sample dilution and matrix interference. Based on these features, the detection sensitivity is greatly improved, and the average signal-to-noise (S/N) ratio is about 20 : 1 of single-cell peaks in the TIC of ILCEI-MS. A high detection throughput of 51 cells per min was achieved by ILCEI-MS for the single-cell metabolic profiling of multiple cell lines, and 368 cellular metabolites were identified. Further, more than 4000 primary single cells digested from the fresh multi-organ tissues of mice were detected by ILCEI-MS, demonstrating its applicability and reliability.

Individuals redistribution based on differential evolution for covariance matrix adaptation evolution strategy.

Among population-based metaheuristics, both Differential Evolution (DE) and Covariance Matrix Adaptation Evolution Strategy (CMA-ES) perform outstanding for real parameter single objective optimization. Compared with DE, CMA-ES stagnates much earlier in many occasions. In this paper, we propose CMA-ES with individuals redistribution based on DE, IR-CMA-ES, to address stagnation in CMA-ES. We execute experiments based on two benchmark test suites to compare our algorithm with nine peers. Experimental results show that our IR-CMA-ES is competitive in the field of real parameter single objective optimization.

A Nomogram Estimation for the Risk of Microvascular Invasion in Hepatocellular Carcinoma Patients Meeting the Milan Criteria.

OBJECTIVE: We aimed to develop and validate a nomogram for preoperatively estimating the risk of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) within the Milan criteria. METHODS: The clinical data of 312 HCC patients who underwent liver surgery at the xxx from Jan 2017 to Dec 2019 were retrospectively collected. Then, the study population was categorized into the training and validation group based on the date of surgery. To identify risk factors related to MVI, we conducted a series of logistic regression analyses. By combining these risk factors, a nomogram was then established. We further clarified the usability of our model through the area under the ROC curve (AUC), decision curve analysis (DCA), and calibration curve. RESULTS: Pathological examination revealed MVI in 108 patients with HCC (34.6%). Three independent predictors were identified: level of alpha-fetoprotein (AFP) exceeds 194 ng/mL (OR = 2.20, 95% CI: 1.13-4.31, p = 0.021), size of tumor (OR = 1.59; 95% CI: 1.18-2.12; P < 0.001) and number of tumors (OR = 3.37, 95% CI: 1.64-7.28, p < 0.001). A nomogram was subsequently built with an AUC of 0.73 and 0.74 respectively in the training cohort and validation cohort. The calibration curve showed a relatively high consistency between predicted probability and observed outcomes. Besides, the DCA revealed that the model was clinically beneficial for preoperatively predicting MVI in HCC. CONCLUSIONS: A model for evaluating the risk of MVI HCC patients was developed and validated. The model could provide clinicians with a relatively reliable basis for optimizing treatment decisions.

Stereotactic body radiation therapy versus radiofrequency ablation in patients with small hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: This study aimed to compare the clinical outcomes and toxicity between small hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT) and those treated with radiofrequency ablation (RFA). METHODS: We searched databases for relevant clinical studies. The primary outcomes of interest were overall survival (OS) at 1 and 2 years, freedom from local progression (FFLP) rate at 2 years, and complications. RESULTS: Five cohorts from 5 retrospective studies and 4,814 patients with HCC were included. Pooled OS at 2 years was significantly lower for SBRT than for RFA [odds ratio (OR): 0.63; 95% confidence interval (CI): 0.51-0.79; P<0.0001], but the pooled FFLP rate at 2 years was higher for SBRT than for RFA (OR: 1.66; 95% CI: 1.05-2.61; P=0.03). In addition, there was no significant difference in the local and liver toxicities of the two treatments. The contradictory conclusion between the OS and FFLP outcome may be attributed to the difference in radiological dose and location, but there were no uniform criteria to illustrate the radiological dose and location in the included studies. CONCLUSIONS: SBRT had a higher local control ratio but poorer prognosis than RFA in patients with small HCC. The local toxicity was comparable in both treatments. Further trials should be designed with uniform standards for SBRT and RFA treatments.

Comparison and development of advanced machine learning tools to predict nonalcoholic fatty liver disease: An extended study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a public health challenge and significant cause of morbidity and mortality worldwide. Early identification is crucial for disease intervention. We recently proposed a nomogram-based NAFLD prediction model from a large population cohort. We aimed to explore machine learning tools in predicting NAFLD. METHODS: A retrospective cross-sectional study was performed on 15 315 Chinese subjects (10 373 training and 4942 testing sets). Selected clinical and biochemical factors were evaluated by different types of machine learning algorithms to develop and validate seven predictive models. Nine evaluation indicators including area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), accuracy, positive predictive value, sensitivity, F1 score, Matthews correlation coefficient (MCC), specificity and negative prognostic value were applied to compare the performance among the models. The selected clinical and biochemical factors were ranked according to the importance in prediction ability. RESULTS: Totally 4018/10 373 (38.74%) and 1860/4942 (37.64%) subjects had ultrasound-proven NAFLD in the training and testing sets, respectively. Seven machine learning based models were developed and demonstrated good performance in predicting NAFLD. Among these models, the XGBoost model revealed the highest AUROC (0.873), AUPRC (0.810), accuracy (0.795), positive predictive value (0.806), F1 score (0.695), MCC (0.557), specificity (0.909), demonstrating the best prediction ability among the built models. Body mass index was the most valuable indicator to predict NAFLD according to the feature ranking scores. CONCLUSIONS: The XGBoost model has the best overall prediction ability for diagnosing NAFLD. The novel machine learning tools provide considerable beneficial potential in NAFLD screening.

Ubiquitin-related molecular classification and risk stratification of hepatocellular carcinoma.

The roles of ubiquitin-related genes in hepatocellular carcinoma (HCC) have not been thoroughly investigated. This study aimed to systematically examine ubiquitin-related genes and identify subtypes and stratify prognosis of HCC by using ubiquitin-related signatures. Survival, biological processes, tumor microenvironment (TME), and genomic alterations of the HCC subtypes were investigated. Patients with HCC were classified into two subtypes (clusters 1 and 2) with distinct survival outcomes, pathways, and genomic alterations. Cluster 2 had better prognosis than did cluster 1. Hepatitis B, hepatitis C, Janus tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, and natural killer cell-mediated cytotoxicity were enriched in cluster 1. Moreover, cluster 2 had a higher immune score and immune cell infiltrations, whereas cluster 1 had a lower immune score and immune infiltrations. Additionally, mutations, amplifications, and deletions among the phosphatidylinositol 3-kinase (PI3K)-AKT, p53, and receptor tyrosine kinase (RTK)-RAS pathways more frequently occurred in cluster 1, while those among the Hippo, MYC, and Notch signaling pathways were found in cluster 2. Finally, a prognostic signature, consisting of eight ubiquitin-related genes, was established and validated. In brief, our study established a new classification and developed a prognostic signature for HCC.

Circular RNA Microarray Analyses in Hepatic Ischemia-Reperfusion Injury With Ischemic Preconditioning Prevention.

Ischemic preconditioning (IPC) represents an effective intervention to relieve hepatic ischemia-reperfusion injury (IRI). Systematic detection of circRNA expression revealing the protection effect of IPC still remains to be elucidated. Here, we applied a microarray to detect circRNA and mRNA expression in ischemic liver with and without IPC (n = 3 in each group). Compared with the sham group, there were 39 circRNAs and 432 mRNAs increased and 38 circRNAs and 254 mRNAs decreased (fold change ≥1.5, P < 0.05) in the group of hepatic IRI. As the result of IPC intervention, 43 circRNAs and 64 mRNAs were increased, and 7 circRNAs and 31 mRNAs were decreased in the IPC group when compared with IRI. We then identified circRNA_017753 as the most possible target that may closely relate to IPC protective signaling and predicted Jade1 as the target related to circRNA_017753. Three possible circRNA-miRNA-mRNA axes were constructed that may play a vital role in protective mechanisms in IPC. The study for the first time systematically detects the dysregulated circRNAs and mRNAs in response to hepatic IRI and IPC intervention. Our profile and bioinformatic analysis provide numerous novel clues to understanding the pathophysiologic mechanism of IPC protection against hepatic IRI.

Identification of an immune-related RNA-binding protein signature to predict survival and targeted therapy responses in liver cancer.

RNA-binding proteins (RBPs) play crucial roles in multiple cancers. However, very few RBPs and their association with immune genes have been systematically studied in liver cancer (LC). We aimed to identify an immune-related RBP signature to predict the survival of LC patients. Bioinformatics methods were used to identify differentially expressed, immune-related, and prognostic RBPs and to develop an immune-related RBP signature based on data from the Cancer Genome Atlas (TCGA) cohort. We obtained eight differentially expressed, immune-related, and prognostic RBPs to construct a risk signature. The signature could effectively distinguish between high- and low-risk patients, and its predictive capacity was validated in the International Cancer Genomics Consortium (ICGC) cohort. We speculated that the high-risk group was more sensitive to targeted therapy. The immune-related RBP signature is an independent prognostic biomarker for LC patients and can expand the application of targeted therapy through patient stratification.

Risk of malignancy and prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors.

BACKGROUND: Small nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) ≤2 cm have variable biological features, and there is no gold standard treatment for their management. The present study aimed to evaluate the risk of malignancy of small NF-PNETs and their outcomes following curative resection. METHODS: Patients with NF-PNETs undergoing surgical resection at the First Affiliated Hospital, College of Medicine, Zhejiang University, between 2012 and 2017 were included. Clinicopathological characteristics, perioperative results, and prognosis were retrospectively analyzed. RESULTS: A total of 73 patients were identified, including 28 with small NF-PNETs and 45 large PNETs; 32.1% of NF-PNETs ≤2 cm underwent a parenchyma-sparing pancreas surgery, which was >6.7% in large NF-PNETs. No statistically significant differences in perioperative results, postoperative complications, and long-term outcomes were found between small tumors undergoing standard and parenchyma-sparing pancreatectomy. Eighteen small tumors (64.3%) developed a perioperative complication, with a clinically significant pancreatic fistula rate of 25%; however, only 2 patient needed reintervention. Small NF-PNETs in 3 patients were malignant. Multivariate logistic regression showed that grade ≥3 and lymphovascular invasion were independently related to malignancy in NF-PNETs. CONCLUSIONS: Small NF-PNETs (≤2 cm) are not immune from potential malignancy. Surgical resection may be considered for small tumors and can provide favorable postoperative and long-term outcomes. Parenchyma-sparing pancreatectomy may be an alternative surgery for selected small local NF-PNETs.

Epstein-Barr virus-negative inflammatory pseudotumor-like variant of follicular dendritic cell sarcoma of the liver: A case report and literature review.

Follicular dendritic cell sarcoma (FDCS) can be divided into the conventional type, and the inflammatory pseudotumor (IPT)-like variant type. Epstein-Barr virus (EBV) infection is considered to be closely associated with the pathogenesis of IPT-like variant of FDCS. Hepatic FDCS has an exceedingly low incidence of only 29 cases reported, with most of these tumors being classified as the IPT-like type. We report a case of an IPT-like variant of FDCS of the liver in a 61-year old man who presented with no marked symptoms. The patient underwent laparoscopic surgery for the mass and was well during a 13-month follow-up periods. The postoperative pathological examination found a proliferation of spindle cells and a diffuse infiltration of inflammatory cells within the tumor. Immunohistochemistry revealed that neoplastic cells were positive for CD23, clusterin, fascin, and PD-L1, and weakly positive for CD35, SMA, and D2-40. The infiltrating lymphocytes were strongly positive for PD1, and IgG4-positive plasma cells were less than 10 cells/high-power field. In situ hybridization for Epstein-Barr virus encoded RNA (EBER) was negative. To our knowledge, the present case is the second case of hepatic IPT-like variant of FDCS without EBV involvement, indicating that EBV infection is not an absolute prerequisite for a diagnosis of the IPT-like variant of FDCS.

Development and validation of a clinical and laboratory-based nomogram to predict nonalcoholic fatty liver disease.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease in China. The early identification and management of patients at risk are essential. We aimed to develop a novel clinical and laboratory-based nomogram (CLN) model to predict NAFLD with high accuracy. METHODS: We designed a retrospective cross-sectional study and enrolled 21,468 participants (16,468 testing and 5000 validation). Clinical information and laboratory/imaging results were retrieved. Significant variables independently associated with NAFLD were identified by a logistic regression model, and a NAFLD prediction CLN was constructed. The CLN was then compared with four existing NAFLD-related prediction models: the fatty liver index (FLI), the hepatic steatosis index (HSI), the visceral adiposity index (VAI) and the triglycerides and glucose (TyG) index. Area under the receiver operator characteristic curve (AUROC) and decision curve analysis (DCA) were performed. RESULTS: A total of 6261/16,468 (38.02%) and 1759/5000 (35.18%) participants in the testing and validation datasets, respectively, had ultrasound-proven NAFLD. Six variables were selected to build the CLN: body mass index (BMI), diastolic blood pressure (DBP), uric acid (UA), fasting blood glucose (FBG), triglyceride (TG), and alanine aminotransferase (ALT). The diagnostic accuracy of the CLN for NAFLD (AUROC 0.857, 95% CI 0.852-0.863) was significantly superior to that of the FLI (AUROC 0.849, 95% CI 0.843-0.855), the VAI (AUROC 0.752, 95% CI 0.745-0.760), the HSI (AUROC 0.828, 95% CI 0.822-0.834), and the TyG index (AUROC 0.774, 95% CI 0.767-0.781) (all p < 0.001). DCA confirmed the clinical utility of the CLN. CONCLUSIONS: This physical examination and laboratory test-based, nonimage-assisted novel nomogram has better performance in predicting NAFLD than the FLI, the VAI, the HSI and the TyG index alone. This model can be used as a quick screening tool to assess NAFLD in the general population.

MicroRNA-191 regulates differentiation and migration of mesenchymal stem cells and their paracrine effect on angiogenesis.

MicroRNAs (miRNAs) are critical regulators in organ development. Among them, miR-191 is known to be regulated in early embryogenesis and dysregulated in cancer. This role in undifferentiated tissues suggests a possible part of miR-191 also in bone marrow derived mesenchymal stem cells (BMSCs) physiology. Here, we report that miR-191 decreased MMP expression and migration of BMSCs. Conditioned media of miR-191 overexpressing BMSCs block VEGF expression, and inhibit angiogenesis of HUVECs. Under osteogenic culture conditions, inhibition of miR-191 significantly induces bone formation. Moreover, our studies showed miR-191 might influence chondrogenesis of BMSCs by directly targeting CCAAT Enhancer Binding Protein Beta (CEBPB). Taken together, here we demonstrate the role of miR-191 in differentiation, migration and paracrine function of BMSCs.

PACAP neuropeptide promotes Hepatocellular Protection via CREB-KLF4 dependent autophagy in mouse liver Ischemia Reperfusion Injury.

Organ ischemia reperfusion injury (IRI), associated with acute hepatocyte death, remains an unresolved problem in clinical orthotopic liver transplantation (OLT). Autophagy, an intracellular self-digesting progress, is responsible for cell reprograming required to regain post-stress homeostasis. Methods: Here, we analyzed the cytoprotective mechanism of pituitary adenylate cyclase-activating polypeptide (PACAP)-promoted hepatocellular autophagy in a clinically relevant mouse model of extended hepatic cold storage (4 °C UW solution for 20 h) followed by syngeneic OLT. Results: In contrast to 41.7% of liver graft failure by day 7 post-transplant in control group, PACAP treatment significantly improved graft survival (91.7% by day 14), and promoted autophagy-associated regeneration programs in OLT. In parallel in vitro studies, PACAP-enhanced autophagy ameliorated cellular damage (LDH/ALT levels), and diminished necrosis in H2O2-stressed primary hepatocytes. Interestingly, PACAP not only induced nuclear cAMP response element-binding protein (CREB), but also triggered reprogramming factor Kruppel-like factor 4 (KLF4) expression in IR-stressed OLT. Indeed, CREB inhibition attenuated hepatic autophagy and recreated hepatocellular injury in otherwise PACAP-protected livers. Furthermore, CREB inhibition suppressed PACAP-induced KLF4 expression, whereas KLF4 blockade abolished PACAP-promoted autophagy and neutralized PACAP-mediated hepatoprotection both in vivo and in vitro. Conclusion: Current study documents the essential neural regulation of PACAP-promoted autophagy in hepatocellular homeostasis in OLT, which provides the emerging therapeutic principle to combat hepatic IRI in OLT.

Metastatic renal cell carcinoma to the pancreas and subcutaneous tissue 10 years after radical nephrectomy: a case report.

BACKGROUND: Synchronous renal cell carcinoma metastasizing to the pancreas and subcutaneous tissue is very rare. Unusual metastatic sites require attention during follow-up of renal cell carcinoma. It is extremely rare for renal cell carcinoma to metastasize to the pancreas; it is also very rare for it to metastasize to the subcutaneous tissue and extremely rare for it to synchronously metastasize to the pancreas and subcutaneous tissue almost a decade after radical nephrectomy. It is well known that most pancreatic tumors are primary pancreatic adenocarcinoma. However, the pancreas can also be an uncommon site for metastasis. We present a rare case of synchronous metastasis of renal cell carcinoma to the pancreas and subcutaneous tissue; we believe it to be only the second such case reported to date. CASE PRESENTATION: We describe a case of a 74-year-old Chinese man who was diagnosed with metastatic renal cell carcinoma to the pancreas and subcutaneous tissue at the same time, 10 years after left radical nephrectomy. He received distal pancreatectomy with spleen preservation plus resection of the subcutaneous tissue lesions on the left side of the anterior abdominal wall and right waist. Pathology showed that all resected metastatic tumors were of the clear cell type. The patient was seen in regular follow-up afterward. CONCLUSION: Synchronous metastatic renal cell carcinoma to the pancreas and subcutaneous tissue is very rare, and it might occur after primary tumor resection. Patients must undergo lifelong monitoring and follow-up with regular examination so that any possible metastasis can be detected early. The optimal resection strategy should involve adequate resection margins and maximal tissue preservation of the pancreas, because renal cell carcinoma metastasizing to the pancreas and subcutaneous tissue has a good prognosis with long-term survival.