Journal of gastrointestinal oncology最新文献

Background: Pancreatic cancer represents a significant global health burden. Although dysregulated lipid metabolism and its associated inflammation drive tumorigenesis, their molecular interplay remains incompletely understood. This bioinformatics study investigates lipid metabolism-related genes (LMRGs) for prognostic prediction and treatment guidance in pancreatic cancer.

Methods: LMRGs were obtained from the Gene Set Enrichment Analysis (GSEA) database, while messenger ribonucleic acid (mRNA) expression profiles and clinical information were downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and International Cancer Genome Consortium (ICGC) databases. Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression analysis were employed to screen prognosis-related genes, followed by the construction of a risk prediction model. Patients were stratified into high- and low-risk groups for prognosis and immune infiltration comparison. Potential therapeutic drugs for pancreatic cancer were predicted using the DSigDB database based on the identified LMRGs.

Results: We successfully established and validated a prognostic prediction model for pancreatic cancer patients based on six LMRGs (AGT, AHR, PLA2G6, PTGS2, TNFRSF21, and VDR). The 1-, 3-, and 5-year area under the receiver operating characteristic (ROC) curve values were 0.623, 0.698, and 0.720, respectively. Immune infiltration analysis showed that after prognostic risk stratification using the six-gene signature, the high-risk group had higher proportions of M0 macrophages and neutrophils. Furthermore, the expression of eight immune checkpoint-related genes was significantly increased in the high-risk group. DSigDB database analysis revealed four possible therapeutic drugs for pancreatic cancer: prolinedithiocarbamate, isoliquiritigenin, aspirin, and resveratrol.

Conclusions: The risk score based on the six LMRGs provides prognostic insights for pancreatic cancer. High-risk pancreatic cancer populations are potentially associated with an immunosuppressive microenvironment. Candidate drugs screened based on LMRGs offer new possibilities for personalized treatment of pancreatic cancer.

Background: Hypercalcemia associated with neuroendocrine tumors (NETs) is typically attributed to increased circulating parathyroid hormone-related protein (PTHrP). However, several cases have now been reported in which hypercalcemia is linked to increased serum 1,25-dihydroxyvitamin D [1,25(OH)₂D]. Until now, the source of this ectopic 1,25(OH)₂D production had not been localized.

Case description: A 53-year-old Caucasian woman presented with hypercalcemia secondary to a metastatic grade 2 distal pancreatic NET, accompanied by a 4.6-fold increase in serum 1,25(OH)₂D. Her hypercalcemia responded to high dose prednisolone and normalized after staged resection of her primary tumor and hepatic metastases. 1,25(OH)₂D levels also normalized with reduction in tumor load. Immunofluorescence of both primary tumor and a hepatic metastasis showed positive expression of 1-alpha hydroxylase, the enzyme that converts 25-hydroxyvitamin D (25OHD) into 1,25(OH)₂D, in tumor cells. High expression was also observed in tumor-associated macrophages (TAMs).

Conclusions: Conversion of 25OHD into 1,25(OH)₂D by 1-alpha hydroxylase represents a lesser-known NET-associated hypercalcemia. This is the first case to localize 1-alpha hydroxylase expression in NETs, and also to report its expression in TAMs. Given that this form of hypercalcemia is responsive to glucocorticoid therapy, measurement of serum 1,25(OH)₂D should be considered in patients with NET presenting with hypercalcemia. Furthermore, these findings highlight a potential role for TAMs in ectopic hormone production and suggest they may serve as therapeutic targets in 1,25(OH)₂D-mediated malignancy-associated hypercalcemia.

Background: Colorectal cancer (CRC) is the third most common malignancy worldwide, and bevacizumab is the backbone antibody against vascular endothelial growth factor (VEGF) for patients with liver metastases. Nevertheless, no clinically applicable biomarker reliably foretells who will benefit, because VEGF expression alone shows limited predictive value. This study aims to discover and functionally validate a molecular signature that can anticipate bevacizumab response and long-term outcome in CRC.

Methods: A total of 620 CRC cases with documented heterogeneous bevacizumab exposure were extracted from The Cancer Genome Atlas (TCGA). Multi-omics layers-whole-exome sequencing, RNA-seq, reverse-phase protein array, immune-deconvolution algorithms [Tool for Immune Estimation Resource 2 (TIMER2), QUANTitative Immunogeneic Sequencing (QUANTISEQ), Estimating the Proportions of Immune and Cancer cells (EPIC), Microenvironment Cell Populations (MCP)-counter], microsatellite instability (MSI) and tumor mutational burden (TMB)-were integrated. Pan-cancer enrichment [Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG)], survival modelling, and nomogram construction were performed, followed by lentiviral over-expression and CRISPR-knockout studies in HT29 and COLO205 cells for proliferation, colony formation, trans-well migration and sphingolipid signaling interrogation.

Results: Actin-like 6B (ACTL6B) emerged as the top predictor, showing inverse correlation with mesenchymal markers and positive association with CD4⁺ cytotoxic infiltration. High ACTL6B transcript consistently predicted better objective response rate (ORR; 67% vs. 31%, P=0.002) and longer median overall survival [OS; hazard ratio (HR) =0.58, 95% confidence interval (CI): 0.41-0.81] and recurrence-free survival (RFS; HR =0.62, 95% CI: 0.44-0.87) in the discovery and two validation sets. Mechanistically, ACTL6B transcriptionally repressed sphingosine-1-phosphate receptor 3 (S1PR3) and activated protein phosphatase 2 regulatory subunit Bbeta (PPP2R2B), thereby dampening pro-migratory sphingosine-1-phosphate signaling. A three-gene logistic model (ACTL6Blow/S1PR3high/PPP2R2Blow) yielded an AUC of 0.84 (95% CI: 0.79-0.89) for progressive disease under bevacizumab.

Conclusions: ACTL6B, alone or combined with S1PR3 and PPP2R2B, constitutes a robust biomarker panel for stratifying CRC patients likely to benefit from bevacizumab, warranting prospective clinical qualification.

Gastric outlet obstruction (GOO) is a common complication in stage IV gastric cancer, often causing malnutrition and delaying conversion therapy. Compared with conventional gastrojejunostomy (CGJ), stomach-partitioning gastrojejunostomy (SPGJ) offers advantages in improving oral intake and reducing gastric emptying disorders. In clinical practice, we found that performing No. 4sb lymph node dissection during the initial bypass procedure improves the surgical field for subsequent radical resection, eliminating the need to reoperate around the anastomosis and greater curvature. This significantly shortens operative time and facilitates recovery. We termed this approach as modified laparoscopic stomach-partitioning gastrojejunostomy (M-LSPGJ), incorporating No. 4sb lymph node dissection, gastrojejunostomy, and Braun anastomosis. In this retrospective study, 22 patients with stage IV gastric cancer and GOO underwent M-LSPGJ followed by conversion therapy with SOX (S-1 + oxaliplatin) or XELOX (capecitabine + oxaliplatin) plus programmed death-1 (PD-1) inhibitors. By postoperative day 30, 86.4% (19/22) resumed normal oral intake [Gastric Outlet Obstruction Scoring System (GOOSS) score =3], with a mean time to reach GOOSS score 2 of 4.5±2.1 days. Nine patients (40.9%) underwent second-stage radical gastrectomy, with R0 resection achieved in 8 (36.4%). The median overall survival (OS) for the entire cohort was 15.0 months. In patients who achieved R0 resection, the median OS was 30.5 months, compared to 10.4 months in the non-R0 group [hazard ratio (HR) =0.18, P=0.008]. M-LSPGJ effectively relieves symptoms and creates favorable conditions for curative resection in selected advanced gastric cancer patients, serving as a promising bridge from palliation to oncologic conversion.

Background: Recent randomized controlled trials have established chemoimmunotherapy as the standard of care for patients with advanced biliary cancers with a median overall survival (OS) of about thirteen months. No data exist to demonstrate the safety and efficacy of liver-directed radiotherapy (RT) for extrahepatic and intrahepatic cholangiocarcinoma (CCA) in the era of chemoimmunotherapy. The purpose of this study is to report our early experience treating patients with CCA using RT and chemoimmunotherapy.

Methods: Twenty-eight patients with CCA who received chemoimmunotherapy sequentially and/or concurrently with RT were retrospectively analyzed. The median biologic equivalent dose (BED) of RT was 84.0 [interquartile range (IQR) 81.4-98.0] Gy. For each patient, we tabulated demographic, disease, and treatment characteristics, including kinetic assessment of laboratory values. The primary goal was to assess acute and late toxicities. Secondary goals were to measure OS using the Kaplan-Meier method and local control using cumulative incidence curves, considering death as a competing risk for local failure. We explored clinical and pathological associations with outcomes.

Results: Most patients (89%) experienced acute low-grade RT toxicities. There were no grade three acute toxicities. Two patients experienced late toxicities potentially attributable to RT. One patient experienced grade two hepatic impairment and another patient experienced grade three pneumonitis. The median OS measured from time of RT completion to death was 17.4 months, and the cumulative incidence of local failure for our patient population was 11% [95% confidence interval (CI): 2.7-26%] at six months, 24% (95% CI: 9.3-43%) at 12 months, and 30% (95% CI: 12-50%) at 24 months. Exploratory analyses indicated that patients whose absolute lymphocyte count recovered faster three months after RT had better survival outcomes [hazard ratio (HR) 0.11 (95% CI: 0.021-0.56, P=0.02)]. Presence of portal vein thrombus (P=0.04) and evidence of liver dysfunction on laboratory values [e.g., increased aspartate aminotransferase (AST) (P=0.005), direct bilirubin (P<0.001), and total bilirubin (P<0.001)] associated with worse OS.

Conclusions: RT appears safe for patients with CCA who receive chemoimmunotherapy, with promising survival outcomes. Immune kinetics and other standard clinicopathological features may identify important prognostic differences amongst patients and help guide management decisions.

Background: Extramedullary multiple myeloma (EMM) is defined by the infiltration of malignant plasma cells into non-osseous tissues. Its co-occurrence with hilar cholangiocarcinoma remains extraordinarily rare. This diagnostic overlap poses substantial clinical risks, as misclassification of EMM as biliary carcinoma may lead to inappropriate surgical interventions and delayed systemic therapy, ultimately compromising patient survival. Therefore, we report this case of misdiagnosis to help reduce the rate of misdiagnoses in the future.

Case description: A 72-year-old male with λ multiple myeloma (MM) (type III, Group B) presented with painless jaundice and weight loss. Laboratory findings revealed obstructive jaundice [total bilirubin (TBIL) 312.3 mg/dL, direct bilirubin (DBIL) 161.5 mg/dL] and elevated carbohydrate antigen 19-9 (CA19-9) (130.5 U/mL). Contrast-enhanced computed tomography (CT) demonstrated a 3 cm hilar mass with peripheral ductal dilation, and magnetic resonance cholangiopancreatography (MRCP) showed abrupt biliary stricture. Despite radiographic features mimicking cholangiocarcinoma, considering the patient's history of myeloma, our team selected CT-guided biopsy of the hilar bile duct tumor. Immunohistochemical analysis confirmed syndecan-1 (CD138)(3+)/cluster of differentiation 38 (CD38)(1+)/cluster of differentiation 3 (CD3)(+)/λ-restricted plasma cell infiltration. The patient was diagnosed with EMM complicated with hilar bile duct metastasis. Subsequently, the patient avoided unnecessary surgical procedures and received proper treatment in the hematology department.

Conclusions: This represents the first documented case of EMM metastasizing to the hilar bile duct, underscoring crucial diagnostic considerations. In patients presenting with hepatic hilar masses-particularly those with a history of MM-hematological malignancies must be included in the differential diagnosis. A multidisciplinary diagnostic approach integrating histopathological analysis, serum biomarkers, and advanced imaging modalities can effectively prevent unnecessary surgical interventions while optimizing therapeutic outcomes.

Background: Liver cancer attributable to hepatitis B virus (HBV) is a malignant tumor of the liver caused by the HBV that imposes an enormous global health burden. This study examined the global, regional, and national trends in incidence, mortality, and disability-adjusted life years (DALYs) for liver cancer attributable to HBV in individuals aged 55 years and older from 1990 to 2021 and the projections to 2035.

Methods: We obtained raw data according to Global Burden of Disease (GBD) 2021 study and used estimated annual percentage change (EAPC) to assess changes in age-standardized incidence, mortality, and DALYs rates. The relationship between disease burden and sociodemographic indices (SDIs) was further analyzed. Finally, Bayesian age-period-cohort (BAPC) modeling was used to predict trends over the 14 years following 2021.

Results: The global burden of liver cancer attributable to HBV among middle-aged and older adults remains substantial, with 127,408.8 incident cases reported in 2021, representing a 120.2% increase compared to 1990 levels. The age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR) were 8.6, 8.0, and 191.5, respectively. There were significant differences between regions, with the highest burden in the middle SDI regions and the lowest in the low-middle SDI regions. The age-stratified analysis revealed a progressive increase in ASIR with advancing age, peaking at 10.49 in the 85 to 89-year group. The BAPC projections indicated that ASIR, ASMR, and ASDR will continue to decline globally in middle-aged and older adult patients with liver cancer attributable to HBV on a flat basis, with a reduced burden on society.

Conclusions: From 1990 to 2021, the ASIR of liver cancer attributable to HBV among adults aged 55 years and older showed a declining trend globally and nationally. However, the absolute number of cases continued to rise due to population growth and aging demographics. Moreover, the risk burden increased with age, and thus greater attention should be paid to liver cancer attributable to HBV in middle-aged and older adults.

Background: Early screening for colorectal cancer (CRC) is crucial for improving patient survival rates and reducing treatment costs. Screening is the initial risk assessment. Early detection means identifying asymptomatic cancers. Diagnosis is confirming malignancy. Population (stage I-II) was referred in our study with the consistently used "early-stage CRC". However, existing detection methods have certain deficiencies in terms of accuracy, sensitivity, and universality. Therefore, this study aims to develop an advanced machine learning-based approach using routine laboratory test indicators to enhance early CRC screening performance.

Methods: This study first explored the classification effects of various common types of machine learning methods on CRC using laboratory test indicators. Subsequently, different integrated models were compared, and a weighted voting strategy based on an improved sine algorithm-guided dung beetle optimizer [improved sine algorithm-guided dung beetle optimizer with weighted voting (MSADBO-WV)] was proposed. Feature selection for CRC was performed on 45 features in the dataset.

Results: The proposed MSADBO-WV method not only outperformed other integrated learning methods in terms of accuracy but also significantly exceeded the accuracy of ordinary machine learning methods [such as deep forest (DF)]. When the number of features was 26, the model achieved the highest accuracy, with the four evaluation indicators being 98.42%±1.53%, 98.46%±1.51%, 98.42%±1.53%, and 98.42%±1.53%, respectively. The analytical framework proposed in this study can be well used for screening CRC.

Conclusions: MSADBO-WV demonstrates promising performance characteristics for CRC screening and will be further evaluated in prospective clinical validation studies to assist in early CRC screening and prevention strategies.