Pancreatic Cancer and its Attributable Risk Factors in East Asia, Now and Future.

BACKGROUND: The disease burden of pancreatic cancer in East Asia is at a high level, but the epidemiological characteristics of pancreatic cancer in the region have not been systematically studied. METHOD: Joinpoint analysis was used to identify average annual percentage change (AAPC) and annual percentage change (APC) in mortality. Age-period-cohort models were used to analyze age-period cohort effects across countries. Bayesian age-period-cohort (BAPC) analysis was used to project the burden of disease for 2020-2030. RESULTS: Pancreatic cancer mortality in males in Japan (2012-2019, APC = -0.97) and Korea (2012-2019, APC = -0.91) has shown a decreasing trend since 2012 (P < .05). However, China (2016-2019, APC = 3.21), Mongolia (2015-2.019, APC = 2.37), and North Korea (2012-2019, APC = 0.47) showed a significant increase in pancreatic cancer in both genders (P < .05). Risk factors for pancreatic cancer in East Asia remained largely stable between 2010 and 2019. Mortality of pancreatic cancer due to smoking began to decline in areas with high socio-demographic index (SDI), and mortality of pancreatic cancer due to high body mass index and high fasting plasma glucose increased with SDI. The age-standardized mortality for pancreatic cancer in Chinese males is expected to exceed that of Japan and South Korea by 2030, but the disease burden of pancreatic cancer in Japan and South Korea remains at extremely high levels. CONCLUSION: Economically developed countries are beginning to show a decreasing trend in the burden of pancreatic cancer disease, and developing countries are experiencing a rapid increase in the age-standardized death rate (ASDR) of pancreatic cancer.

Porta hepatic schwannoma: case report and a 30-year review of the literature yielding 15 cases.

BACKGROUND: Schwannomas located in the periportal region are extremely rare. Only 14 cases have been reported in the medical literature worldwide. Cases of porta hepatic schwannomas reported in the literature worldwide were reviewed. As a result, it is very challenging for surgeons to make a preoperative diagnosis due to its rarity and nonspecific imaging manifestations. CASE PRESENTATION: A 57-year-old Chinese female was admitted to our institution with complaint of upper abdominal distension and the abdominal CT in the local hospital revealed a hypodense mass in the porta hepatis. A fine needle aspiration (FNA) was made to confirm the diagnosis, but the result was just suggestive of spindle cell neoplasia. Eventually, the patient underwent surgery and postoperative pathology confirmed schwannoma in porta hepatis. The patient recovered uneventfully with no evidence of recurrence after a follow-up period of 41 months. CONCLUSIONS: It is essential for the final diagnosis of porta hepatic schwannomas to combine histological examination with immunohistochemistry after surgery. The main treatment of porta hepatic schwannomas is complete excision with free margins and no lymph node dissection. In some cases, biliary reconstruction or the proper hepatic and the gastroduodenal artery resection was performed because the tumor was inseparably attached to the extrahepatic bile duct or the proper hepatic and the gastroduodenal artery. Malignant transformation of schwannomas is very rare and the overall prognosis is satisfactory.

Inflammatory bowel diseases, interleukin-6 and interleukin-6 receptor subunit alpha in causal association with cerebral cortical structure: a Mendelian randomization analysis.

Background: Neurological involvement and psychiatric manifestations have been documented in clinical cases of inflammatory bowel disease (IBD); however, the presence of a causal relationship remains elusive. The objective of this study is to investigate the modifications occurring in the cerebral cortex as a result of IBD. Methods: A compendium of data extracted from a genome-wide association study (GWAS) involving a maximum of 133,380 European subjects. A series of Mendelian random analyses were applied to exclude heterogeneity and pleiotropy, ensuring the stability of the results. Results: Neither IBDs nor inflammatory cytokines (IL-6/IL-6Rα) were found to have a significant causality with surface area (SA) and thickness (TH) at the global level. At the regional functional brain level, Crohn's disease (CD) significantly decreased the TH of pars orbitalis (ß=-0.003mm, Se=0.001mm, pivw =4.85×10-4). IL-6 was observed to reduce the SA of middle temporal (ß=-28.575mm2, Se=6.482mm2, pivw=1.04×10-5) and increase the TH of fusiform (ß=0.008mm, Se=0.002mm, pivw=8.86×10-5) and pars opercularis (ß=0.009mm, Se=0.002mm, pivw=2.34×10-4). Furthermore, a causal relationship between IL-6Rα and an increase in the SA of superior frontal (ß=21.132mm2, Se=5.806mm2, pivw=2.73×10-4) and the TH of supramarginal (ß=0.003mm, Se=0.0002mm, pivw=7.86×10-37). All results passed sensitivity analysis and no heterogeneity and pleiotropy were detected. Conclusion: The correlation between IBD and changes in cerebral cortical structures implies the existence of a gut-brain axis at the organismal level. It is recommended that clinical patients with IBD prioritize long-term management of inflammation, as changes at the organismal level can lead to functional pathologies. Magnetic resonance imaging (MRI) may be considered as an additional screening option for IBD.

Crosstalk of cuproptosis-related prognostic signature and competing endogenous RNAs regulation in hepatocellular carcinoma.

BACKGROUND: Cuproptosis is a new type of programmed cell death involved in the regulation of neuroendocrine tumors, immune microenvironment, and substance metabolism. However, the role of cuproptosis-related genes (CRGs) in Hepatocellular carcinoma (HCC) remains unclear. METHOD: Through multiple bioinformatics analysis, we constructed a prognostic gene model and competing endogenous RNA (ceRNA) network. The correlation between CRGs and prognosis, immune infiltration, immune checkpoints, microsatellite instability (MSI) and tumor mutational burden (TMB) was analyzed by Kaplan-Meier curve, univariate Cox, multivariate regression, and Spearman's analysis in HCC patients. Besides, the qRT-PCR and immunohistochemistry assays were used to determine prognostic CRGs mRNA and protein expression in HCC. RESULTS: We established a novel 3-gene signature related to CRGs for evaluating the prognosis of HCC patients. HCC patients with high risk scores had a poor prognosis with an area under the curve of 0.737, 0.646, and 0.634 on 1-year, 3-year, and 5-year receiver operating characteristic curves. Significant correlation was observed between prognostic CRGs and immune infiltration, immune checkpoints, MSI and TMB. We also developed five ceRNA networks to regulate the occurrence and progression of HCC. CDKN2A, DLAT, and PDHA1 protein expression was up-regulated in HCC versus normal tissues. Besides, the mRNA expression levels of CDKN2A, DLAT, GLS, and PDHA1 were elevated in the HCC cell lines compared to the normal liver cell lines. CONCLUSIONS: This novel prognostic CRGs signature could be accurately predict the prognosis of patients with HCC. The ceRNA regulatory network might be potential prognostic biomarkers and therapeutic targets for HCC patients.

A six-miRNA signature as a novel biomarker for improving prediction of prognosis and patterns of immune infiltration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-related death. MicroRNAs (miRNAs) belong to a subfamily of functional non-coding RNAs (ncRNAs) and are essential regulators of tumorigenesis. They affect tumor-related therapeutic response, tumor metastasis, and clinical outcomes of several human malignant tumors. However, the prognostic value of miRNAs and their role in the tumor immune microenvironment (TIME) of HCC have not been clarified. MATERIALS AND METHODS: Raw RNA-sequencing data (mRNA and miRNA) and clinicopathological characteristics of HCC samples were downloaded from the TCGA-GDC database. The Perl programming language, R software, Cytoscape software, and several online databases were used to clarify the clinical significance and biological functions of miRNAs and their target genes in HCC. RESULTS: A total of 424 mRNA-sequencing samples and 425 miRNA-sequencing samples were obtained from the TCGA database. There were 344 HCC cases with complete information in the TCGA dataset and they were randomly categorized into two subgroups. Six miRNAs were identified as independent prognostic biomarkers for HCC patients by univariate and multivariate Cox regression analysis. The constructed prognostic signature, which contains these six miRNAs, was significantly correlated with overall survival (OS). In addition, this prognostic signature is superior to single miRNA in predicting short-term prognosis of HCC patients. We also found that the prognostic signature was significantly associated with tumor-related immune cell infiltration, TIME, and immunotherapeutic response. Furthermore, a total of 4568 potential target genes of six miRNAs were identified. The miRNA-mRNA co-expression network, protein-protein interaction (PPI) network, and functional and pathway enrichment analysis demonstrated that these miRNA-related target genes have important biological effects during the initiation and progression of HCC. CONCLUSIONS: This study demonstrates that the miRNA signature can accurately predict the prognosis of HCC patients and provide a basis for novel immunotherapy treatments.

Prognostic Biomarkers and Immunotherapeutic Targets Among CXC Chemokines in Pancreatic Adenocarcinoma.

BACKGROUND: Pancreatic cancer is one of the principal causes of tumor-related death worldwide. CXC chemokines, a subfamily of functional chemotactic peptides, affect the initiation of tumor cells and clinical outcomes in several human malignant tumors. However, the specific biological functions and clinical significance of CXC chemokines in pancreatic cancer have not been clarified. METHODS: Bioinformatics analysis tools and databases, including ONCOMINE, GEPIA2, the Human Protein Atlas, DAVID, GeneMANIA, cBioPortal, STRING, DGidb, MethSurv, TRRUST, SurvExpress, SurvivalMeth, and TIMER, were utilized to clarify the clinical significance and biological functions of CXC chemokine in pancreatic cancer. RESULTS: Except for CXCL11/12, the transcriptional levels of other CXC chemokines in PAAD tissues were significantly elevated, and the expression level of CXCL16 was the highest among these CXC chemokines. Our findings also suggested that all of the CXC chemokines were linked to tumor-immune dysfunction involving the abundance of immune cell infiltration, and the Cox proportional hazard model confirmed that dendritic and CXCL3/5/7/8/11/17 were significantly associated with the clinical outcome of PAAD patients. Furthermore, increasing expressions of CXCL5/9/10/11/17 were related to unfavorable overall survival (OS), and only CXCL17 was a prognostic factor for disease-free survival (DFS) in PAAD patients. The expression pattern and prognostic power of CXC chemokines were further validated in the independent GSE62452 dataset. For the prognostic value of single CpG of DNA methylation of CXC chemokines in patients with PAAD, we identified 3 CpGs of CXCL1, 2 CpGs of CXCL2, 2 CpGs of CXCL3, 3 CpGs of CXCL4, 10 CpGs of CXCL5, 1 CpG of CXCL6, 1 CpG of CXCL7, 3 CpGs of CXCL12, 3 CpGs of CXCL14, and 5 CpGs of CXCL17 that were significantly associated with prognosis in PAAD patients. Moreover, the prognostic value of CXC chemokine signature in PAAD was explored and tested in two independent cohort, and results indicated that the patients in the low-risk group had a better OS compared with the high-risk group. Survival analysis of the DNA methylation of CXC chemokine signature demonstrated that PAAD patients in the high-risk group had longer survival times. CONCLUSIONS: These findings reveal the novel insights into CXC chemokine expression and their biological functions in the pancreatic cancers, which might serve as accurate prognostic biomarkers and suitable immunotherapeutic targets for patients with pancreatic cancer.

Hepatic schwannoma: A case report and an updated 40-year review of the literature yielding 30 cases.

Hepatic schwannoma is a rare benign disease with a good prognosis. Early diagnosis is difficult due to the absence of specific clinical presentations and its rarity. The present study briefly described a 64-year-old female patient with hepatic schwannoma mimicking intrahepatic cholangiocarcinoma. Furthermore, the clinical data of 30 patients with hepatic schwannoma were also reviewed and analyzed. The mean age of the 30 patients was 51.7 years (range, 21-83 years) and ~2/3 were female. All patients in the benign group underwent surgical treatment and survived until the last follow-up, of whom 19 received complete resection and the remaining 1 underwent liver transplantation. However, in the malignant group, only three cases who underwent the surgical resection remained alive at last follow-up. Another seven cases were succumbed to mortality, 4 cases of whom had deteriorated to have no operation opportunity by the time they saw a doctor, and among the remaining three cases with hepatectomy, 1 died of liver dysfunction at 21 days postoperatively, 2 succumbed to recurrences at 18 and 23 months postoperatively. In conclusion, hepatic schwannoma is a rare benign disease with a good prognosis. However, once the malignant transformation occurs, the prognosis is not satisfied. Complete resection is the mainstay for cure and liver transplantation is often necessary.

Carcinosarcoma of the Lesser Omentum: A Unique Case Report and Literature Review.

Carcinosarcoma is a rare tumor consisting of epithelial and mesenchymal components, both of which are histologically malignant. It usually runs an aggressive clinical course, with higher metastatic potential than other kinds of carcinomas or sarcomas.Here, we present an extremely uncommon case of carcinosarcoma occurred in the lesser omental bursa in a 65-year-old Chinese man. Metastasis was observed 2 months after operation and disappeared completely after chemotherapy. Until now, 3 years after surgery, the patient is still alive without any signs or symptoms of recurrence.To our knowledge, this is the first case of carcinosarcoma originated from lesser omentum. Surgical resection and the ifosfamide-based combination chemotherapy may be effective to carcinosarcoma in the lesser omentum.