The prognostic value of age-adjusted Charlson comorbidity index in laparoscopic resection for hilar cholangiocarcinoma.

The prognostic role of the Age-Adjusted Charlson Comorbidity Index (ACCI) in hilar cholangiocarcinoma patients undergoing laparoscopic resection is unclear. To evaluate ACCI's effect on overall survival (OS) and recurrence-free survival (RFS), we gathered data from 136 patients who underwent laparoscopic resection for hilar cholangiocarcinoma at Zhengzhou University People's Hospital between 1 June 2018 and 1 June 2022. ACCI scores were categorized into high ACCI (ACCI > 4.0) and low ACCI (ACCI ≤ 4.0) groups. We examined ACCI's association with OS and RFS using Cox regression analyses and developed an ACCI-based nomogram for survival prediction. Our analysis revealed that higher ACCI scores (ACCI > 4.0) (HR = 2.14, 95%CI: 1.37-3.34) were identified as an independent risk factor significantly affecting both OS and RFS in postoperative patients with hilar cholangiocarcinoma (p < 0.05). TNM stage III-IV (HR = 7.42, 95%CI: 3.11-17.68), not undergoing R0 resection (HR = 1.58, 95%CI: 1.01-2.46), hemorrhage quantity > 350 mL (HR = 1.92, 95%CI: 1.24-2.97), and not receiving chemotherapy (HR = 1.89, 95%CI: 1.21-2.95) were also independent risk factors for OS. The ACCI-based nomogram accurately predicted the 1-, 2-, and 3-year OS rates, with Area Under the Curve (AUC) values of 0.818, 0.844, and 0.924, respectively. Calibration curves confirmed the nomogram's accuracy, and decision curve analysis highlighted its superior predictive performance. These findings suggest that a higher ACCI is associated with a worse prognosis in patients undergoing laparoscopic resection for hilar cholangiocarcinoma. The ACCI-based nomogram could aid clinicians in making accurate predictions about patient survival and facilitate individualized treatment planning.

Expression, oncological and immunological characterizations of BZW1/2 in pancreatic adenocarcinoma.

Background: Despite the progress in early diagnosis and treatment, prognosis of pancreatic adenocarcinoma (PAAD) is still poor. Basic leucine zipper and W2 domain-containing protein 1 (BZW1) and protein 2 (BZW2) are attached to the basic leucine zipper (bZIP) superfamily. Recently, BZW1 was identified as an important role in glycolysis of PAAD. However, the comprehensive reports about BZW1/2 in PAAD are not sufficient. Methods: RNA-seq data in the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were retrospectively analyzed. We explored the expression of BZW1/2 in PAAD tissues and the associations between BZW1/2 and prognosis. In addition, the potential roles of BZW1/2 in tumor microenvironment (TME) of PAAD were analyzed. Finally, clinicopathological data of 49 patients with PAAD in our institution were collected. Immunohistochemistry was used to determine the expression of BZW1/2 in PAAD samples. Results: BZW1 and BZW2 were upregulated in PAAD tissues compared to normal tissues (p < 0.05). The expression of BZW1/2 were not significantly correlated with gender, grade and stage of PAAD (p > 0.05). High expression of BZW2 was an independent predictor for poor prognosis of PAAD (HR 1.834, 95%CI 1.303-2.581, p = 0.001). And a nomogram to predict overall survival (OS) of PAAD was established with a C-index of 0.685. BZW1 and BZW2 expression were positively associated with T cell mediated immune response to tumor cell and Th2 cells in xCell database. Tumor Immune Single-Cell Hub (TISCH) analyses indicated that BZW1 and BZW2 were mainly expressed in B cells and malignant cells. External cohort furtherly validated that high expression of BZW1 and BZW2 were predictors for poor prognosis of PAAD. Conclusion: We found that BZW1 and BZW2 are highly expressed in malignant cells and B cells in the TME of PAAD. BZW2 is an independent predictor for OS of PAAD. BZW1 and BZW2 expression are positively associated with T cell mediated immune response to tumor cell and Th2 cells in PAAD.

Preoperative Oral Carbohydrate Levels in Patients with Type 2 Diabetes Mellitus: The Clinical Guiding Significance of Free Fatty Acids.

Background: It is still controversial whether preoperative oral carbohydrate (POC) should be applied to patients with type 2 diabetes mellitus (T2DM) in the enhanced recovery after surgery (ERAS) protocol. There is no relevant consensus or indicators to provide guidance as to whether T2DM patients should take POC. Methods: In total, 164 T2DM patients who underwent laparoscopic hepatectomy were analyzed. According to the level of blood free fatty acids (FFAs) and whether the patients received POC, the patients were divided into 6 groups: the low FFA carbohydrate group (LFFAC group), low FFA fasting water group (LFFAF group), medium FFA carbohydrate group (MFFAC group), medium FFA fasting water group (MFFAF group), high FFA carbohydrate group (HFFAC group) and high FFA fasting water group (HFFAF group). Results: Patients with low FFA levels showed better perioperative blood glucose control and a lower incidence of postoperative complications than those in the medium and high FFA groups, especially when patients received POC. Further analyses revealed that the postoperative plasma concentrations of IL-6 and TNF-α were significantly decreased in the POC group compared with the fasting water group, except for patients with high FFA levels. Receiver operating characteristic (ROC) curve analysis revealed that when the FFA concentration was higher than 0.745 mmol/L, the risk of poor blood glucose control during the perioperative period was increased. Conclusions: FFAs have clinical guiding significance for the application of POC in patients with T2DM under ERAS administration. T2DM patients with low FFAs are more suitable for receiving POC.

Portal Venous Circulating Tumor Cells Undergoing Epithelial-Mesenchymal Transition Exhibit Distinct Clinical Significance in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Much importance is attached to the clinical application value of circulating tumor cells (CTCs), meanwhile tumor-proximal CTCs detection has interested researchers for its unique advantage. This research mainly discusses the correlation of portal venous (PoV) CTCs counts in different epithelial-mesenchymal transition status with clinicopathologic parameters and postoperative prognosis in resectable pancreatic ductal adenocarcinoma patients (PDAC). METHODS: PDAC patients (n=60) who received radical resection were enrolled in this research. PoV samples from all patients and peripheral venous (PV) samples from 32 patients among them were collected to verify spatial heterogeneity of CTCs distribution, and explore their correlation with clinicopathologic parameters and clinical prognosis. RESULTS: CTCs detectable rate and each phenotype count of PoV were higher than those of PV. Patients with recurrence had higher PV and PoV epithelial CTCs (E-CTCs) counts than recurrence-free patients (P<0.05). Some unfavourable clinicopathologic parameters were closely related to higher PoV CTCs counts. Multivariate regression analysis demonstrated that PoV mesenchymal CTC (M-CTC)s≥1/5 ml was an independent risk factor for metastasis free survival (MFS) (P=0.003) and overall survival (OS) (P=0.043). CONCLUSIONS: Our research demonstrated that portal venous was a preferable vessel for CTC test, and patients with PoV M-CTC≥1/5 ml had shorter MFS and OS time in resectable PDAC patients. PoV CTC phenotype detection has the potential to be a reliable and accurate tool to identify resectable PDAC patients with high tendency of postoperative metastasis for better stratified management.

Identification of Critical Pathways and Potential Key Genes in Poorly Differentiated Pancreatic Adenocarcinoma.

INTRODUCTION: The poorly differentiated pancreatic adenocarcinoma (PDAC) is an extremely lethal neoplasm without effective biomarkers for early detection and prognosis prediction, which is characteristically unresponsive to chemotherapeutic regimens. This study aims at searching for key genes which could be applied as novel prognostic biomarkers and therapeutic targets in PDAC. METHODS: Clinical samples were collected and a comprehensive differential analysis of seven PDAC samples by integrating RNA-seq data of tumor tissues and matched normal tissues from both our cohort and gene expression profiling interactive analysis (GEPIA) were performed to discover potential prognostic genes in PDAC. Pathway enrichment analysis was carried out to determine the biological function of PDAC differentially expressed genes (DEGs), and protein-protein interaction (PPI) network was constructed for functional modules analysis. Real-time PCR was performed to validate expression of hub genes. RESULTS: A total of 126 PDAC-specific expressed genes identified from seven PDAC samples were predominantly enriched in cell adhesion, integral component of membrane, signal transduction and chemical carcinogenesis, IL-17 signaling pathway, indicating that obtained genes might play a unique role in PDAC tumorigenesis. Furthermore, survival analysis revealed that five genes (CEACAM5, KRT6A, KRT6B, KRT7, KRT17) which exhibited high expression levels in tumor tissues were obviously correlated with the prognosis of PDAC patients and KRT7 was positively correlated with KRT6A, KRT6B, KRT17 expression. In addition, real-time PCR demonstrated that the expression level of the hub genes was consistent with RNA-seq analysis. DISCUSSION: The current study suggested that CEACAM5, KRT6A, KRT6B, KRT7, and KRT17 may represent novel prognostic biomarkers as well as novel therapeutic targets for poorly differentiated PDAC.

Identification of critical pathways and potential therapeutic targets in poorly differentiated duodenal papilla adenocarcinoma.

BACKGROUND: Duodenal papilla carcinoma (DPC) is a rare malignancy of the gastrointestinal tract with high recurrence rate, and the pathogenesis of this highly malignant neoplasm is yet to be fully elucidated. This study aims to identify key genes to further understand the biology and pathogenesis underlying the molecular alterations driving DPC, which could be potential diagnostic or therapeutic targets. METHODS: Tumor samples of three DPC patients were collected and integrating RNA-seq analysis of tumor tissues and matched normal tissues were performed to discover differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were carried out to understand the potential bio-functions of the DPC differentially expressed genes (DEGs). Protein-protein interaction (PPI) network was constructed for functional modules analysis and identification of hub genes. qRT-PCR of clinical samples was conducted to validate the expression level of the hub genes. RESULTS: A total of 110 DEGs were identified from our RNA-seq data, GO and KEGG analyses showed that the DEGs were mainly enriched in multiple cancer-related functions and pathways, such as cell proliferation, IL-17signaling pathway, Jak-STAT signaling pathway, PPAR signaling pathway. The PPI network screened out five hub genes including IL-6, LCN2, FABP4, LEP and MMP1, which were identified as core genes in the network and the expression value were validated by qRT-PCR. The hub genes identified in this work were suggested to be potential therapeutic targets of DPC. DISCUSSION: The current study may provide new insight into the exploration of DPC pathogenesis and the screened hub genes may serve as potential diagnostic indicator and novel therapeutic target.

Predictive significance of tumor budding in postoperative liver metastasis of pancreatic neuroendocrine tumors.

BACKGROUND: Although pancreatic neuroendocrine tumors (PNETs) are considered indolent tumors, nearly half of cases metastasize to the liver, which can be lethal. However, effective indicators to predict aggressive behavior have not been well-established. METHODS: In the current study, we explored the prognostic significance of tumor budding in Grade 1-2 PNETs. Hematoxylin-eosin and immunohistochemically stained slides of surgically removed Grade 1-2 PNETs were evaluated. RESULTS: Tumor budding, a histomorphological parameter that corresponds to single cells or small cell clusters (<5 cells), was classified as low (0-10 buds) and high (>10 buds) grade. We observed that tumor budding was correlated with aggressive histopathological parameters, such as T stage, lymph node status, metastasis, and vascular invasion (p < .05). Univariate and multivariate analyses showed that high-grade budding was an independent predictive factor for postoperative liver metastasis (p = .012). Moreover, Grade 1-2 PNETs with high-grade budding was associated with worse overall survival and disease-free survival (p = .0015 and p = .0041, respectively). CONCLUSIONS: We conclude that tumor budding may serve as a valuable parameter in the risk stratification of postoperative liver metastasis and that incorporating tumor budding into histopathological reports may aid in appropriate clinical management.