World Journal of Gastrointestinal Oncology最新文献

Background: The incidence of early-onset colorectal cancer (EOCRC, < 45 years of age at onset) is on the rise among adults, including African Americans (AA).

Aim: To examine differences between EOCRC and late-onset colorectal cancer (LOCRC) among AA patients and any effect during coronavirus disease (COVID) by comparing data during pre-COVID (2015-2019) and the COVID era (2020-2023).

Methods: We conducted a retrospective review of Howard University Hospital records from 2015 to 2023 for colorectal cancer patients that included demographics, clinicals, pathology, and colonoscopy records. A three-year interval analysis was performed to compare post-COVID era (2020-2023) to preceding years to discern temporal trends.

Results: The study included 138 LOCRC and 13 EOCRC cases of which > 80% of patients were AA. Compared to pre-COVID, LOCRC cases increased in number from 55 to 83, and EOCRC cases increased from 6 to 7 during COVID. There was no change in mean age for LOCRC (64.7 years vs 65.3 years) but mean age increased for EOCRC (37.3 years vs 41.5 years). Males predominated in both groups particularly during the pandemic. More than 65% of LOCRC patient colonoscopies were for diagnostic purposes. Gastrointestinal bleeding as a colonoscopy indication and reduced bowel preparation quality were increased during the pandemic. EOCRC patients showed a shift from stage 4 (49.2%) to stage 2 (30%) and LOCRC patients staging trends changed from stage 4 (40%) to stage 3 (28.6%).

Conclusion: We report increase in colorectal cancer cases during the COVID-19 era, especially among young AA males. EOCRC and LOCRC patients showed distal location predominance, most commonly in recto-sigmoid region. The decrease in staging or metastasis, which might be due to growing awareness and earlier detection among patients.

Background: Gastrointestinal tumors are among the most common and deadly cancers globally, with radiotherapy and bevacizumab being key treatment strategies. Radiotherapy uses high-energy radiation to target DNA, reducing tumor size and alleviating symptoms. Bevacizumab, a targeted therapy, inhibits angiogenesis and tumor growth, particularly in advanced gastrointestinal cancers. However, both treatments can cause adverse gastrointestinal effects, such as intestinal mucosal damage and perforation. While research on the risk of intestinal perforation has grown, the underlying mechanisms remain underexplored. This study aims to compare the incidence of intestinal perforation and survival rates in patients treated with radiotherapy combined with bevacizumab vs bevacizumab alone.

Aim: To investigate the effect of radiotherapy on the risk of intestinal perforation in patients with colon cancer treated with bevacizumab.

Methods: A total of 70 patients diagnosed with gastrointestinal malignancies admitted to our hospital from January 2023 to December 2024 were selected as research subjects. According to different treatment methods, 70 patients were divided into the bevacizumab only group (receiving bevacizumab treatment) and the bevacizumab + radiotherapy group (receiving radiotherapy combined with bevacizumab treatment), with 35 cases in each group. The two groups were compared in terms of clinical efficacy, incidence of intestinal perforation, serum tumor marker levels, overall survival and progression-free survival, levels of angiogenic factors, and adverse reactions.

Results: Compared with the group treated with bevacizumab alone, the group treated with bevacizumab plus radiotherapy showed significant improvements in effective rate, overall survival, and progression-free survival (P < 0.05); the probability of intestinal perforation in the bevacizumab + radiotherapy group was 13.33%, while the probability of intestinal perforation in the bevacizumab group was 0. There was a statistically significant difference in the incidence of intestinal perforation between the two groups (P = 0.039). Following treatment, the levels of carbohydrate antigen (CA) 125, CA199, and CA153 in patients were significantly reduced (P < 0.05).

Conclusion: Radiation therapy may increase the risk of intestinal perforation in colon cancer patients receiving bevacizumab treatment. In clinical applications, the risks of combined use of radiotherapy and bevacizumab should be fully considered and personalized treatment plans should be formulated.

Background: Immune checkpoint inhibitors have demonstrated significant efficacy in colorectal cancer (CRC) patients with microsatellite instability-high or deficient mismatch repair. However, their efficacy as monotherapy is limited in microsatellite stable/proficient mismatch repair (MSS/pMMR) subtypes.

Aim: To provide an evidence-based rationale for optimizing later-line therapeutic strategies in advanced MSS/pMMR CRC.

Methods: This study conducted a systematic retrospective analysis to evaluate the efficacy and safety of a triple-combination regimen comprising programmed death 1 inhibitors, fruquintinib and docetaxel administered as third-line therapy in 13 patients with advanced MSS/pMMR CRC.

Results: Primary endpoints included progression-free survival and disease control rate. Intention-to-treat analysis showed median progression-free survival 7.0 months, median overall survival 18.5 months, disease control rate 61.5%, with manageable toxicity.

Conclusion: Although this is a small-sample retrospective study, it preliminarily validates the synergistic effect of programmed death 1 inhibitors combined with fruquintinib and docetaxel in MSS/pMMR CRC, providing a novel strategy with translational significance for later-line treatment in advanced patients.

This letter provides commentary on the manuscript "Intensive care unit outcomes and prognostic factors of colorectal cancer". The study is the first to present multicenter data on the 90-day mortality of patients with colorectal cancer admitted to the intensive care unit, and identifies chemotherapy history, elective surgery, and conventional oxygen therapy as independent prognostic factors. We propose three refinements to enhance the study's clinical utility: Clarify chemotherapy details, including regimen and treatment phase, along with the surgical approach (curative vs palliative) and how preoperative tumor staging influences prognosis; elucidate the relationship between intensive care unit admission etiologies and prognosis; and incorporate colorectal cancer-specific biomarkers to optimize prognostic scoring systems. The study's core contribution is substantial, and refinement of the details will further enhance its clinical translational relevance.

Background: Recurrence remains the leading cause of poor prognosis in hepatocellular carcinoma (HCC), particularly among patients infected with hepatitis B virus (HBV). The telomerase reverse transcriptase (TERT) promoter is the most frequently mutated site in HBV-related HCC; however, its prognostic significance is not fully established.

Aim: To evaluate the prognostic impact of TERT promoter mutations and efficiency of digital polymerase chain reaction (dPCR).

Methods: A total of 66 HBV-related HCC patients who underwent hepatectomy were enrolled in this study. DNA extracted from fresh tumor tissues was analyzed for TERT promoter mutations using Sanger sequencing and dPCR. The dPCR assay was optimized by adding 7-deaza-dGTP, CviQ1, and ethylenediaminetetraacetic acid to improve detection sensitivity. Concordance between methods was assessed, and nomogram survival prediction models were developed to evaluate prognostic value based on mutation status.

Results: TERT promoter mutations were detected in 26/66 (39.39%) cases by Sanger sequencing and 30/66 (45.45%) by dPCR. The two methods showed high concordance (93.939%, κ = 0.876), with dPCR demonstrating 100% sensitivity and 90% specificity. Patients harboring TERT promoter mutations exhibited reduced overall survival and higher recurrence risk. Nomogram models successfully distinguished mutant from non-mutant cases for both overall survival (C-index: 0.7651) and disease-free survival (C-index: 0.6899).

Conclusion: TERT promoter mutation predicts poor prognosis in HBV-related HCC and serves as a biomarker for risk stratification. Optimized dPCR outperforms Sanger sequencing, and nomograms with TERT status guide precision therapy.

Background: Citrullination is a post-translational modification mediated by calcium-dependent peptidylarginine deiminases that results in notable changes in protein structure and function. Glial fibrillary acidic protein (GFAP), which is highly vulnerable to peptidylarginine deiminases-mediated modification, has been found to be elevated in activated hepatic stellate cells, with GFAP-positive hepatic stellate cells and myofibroblasts accumulating within and around areas of hepatic fibrosis. Although recent studies have shown that the expression of citrullinated GFAP (cit-GFAP) increases during hepatic fibrosis, its expression pattern and functional roles in hepatocellular carcinoma (HCC) remain unclear.

Aim: To determine whether cit-GFAP expression influences the recurrence and survival of patients undergoing hepatic resection for HCC.

Methods: We retrospectively analyzed 169 patients with HCC who underwent hepatic resection. Based on the immunohistochemical staining of resected specimens, the enrolled patients were stratified into two groups according to cit-GFAP expression: Low (-/1 +) or high (2 +/3 +) levels of expression. Kaplan-Meier survival curves were constructed to assess overall survival and recurrence-free survival, and comparisons between groups were performed using the log-rank test.

Results: The median follow-up duration was 33 months (range, 1-183). High cit-GFAP expression, identified in 81 patients (48.2%), was significantly associated with male sex, hepatitis B virus positivity, and higher Edmonson-Steiner grade. No associations were found between age, diabetes, hypertension, cirrhosis, Child-Pugh classification, major portal vein invasion, hematological or biochemical parameters, tumor size, or number. Patients exhibiting high cit-GFAP expression demonstrated significantly poorer overall survival. Multivariate Cox analysis identified large tumor size (hazard ratio: 2.967; 95% confidence interval: 1.097-8.024; P = 0.032) and high cit-GFAP expression (hazard ratio: 2.753; 95% confidence interval: 1.015-7.464; P = 0.047) as independent predictors of poor postoperative survival. Although recurrence rates were high in patients with high cit-GFAP expression, the difference was not statistically significant.

Conclusion: Following curative resection in patients with HCC, high cit-GFAP expression may serve as a potential prognostic biomarker, although further validation through independent cohort studies is warranted.

Background: Multiple exosomal microRNAs were reported to have a significant role in colorectal cancer (CRC) cells. The function and mechanism of exosomal miR-191 in CRC have not been clearly elucidated.

Aim: To explore the roles of miR-191 in CRC.

Methods: Supernatant exosomes from CRC cells were extracted and identified. After coculture, macrophage polarization was determined using flow cytometry for the markers cluster of differentiation (CD) 68 and CD163, enzyme-linked immunosorbent assay for the cytokines interleukin (IL)-4 and IL-10, western blotting for chitinase-like protein 3 and arginase-1 expression, and immunofluorescent staining for 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate. Reactive oxygen species (ROS) level, ferroptosis-related proteins (SLC7A11 and GPX4), and apoptosis were determined with flow cytometry, western blotting, and TUNEL staining. We performed in vivo experiments to determine the function of exosomal miR-191 and M2 macrophage polarization.

Results: We successfully isolated exosomes from CRC cells. Inhibition of miR-191 in CRC cells suppressed M2 polarization of macrophages. After coculture of macrophages, inhibition of miR-191 induced ROS production, ferroptosis, and apoptosis of CRC cells. Silencing of exosomal miR-191 from CRC cells prevented M2 polarization of macrophages, and weakened CRC development by inducing ferroptosis. Exosomal miR-191 accelerated cancer progression in CRC nude mice by promoting M2 polarization of macrophages.

Conclusion: Inhibition of exosomal miR-191 attenuated CRC progression by inducing ferroptosis in macrophages. This study revealed a novel mechanism by which exosomal miR-191 modulates the tumor microenvironment.

Background: Inflammatory cytokines are associated with cancer prognosis, but their specific role in cholangiocarcinoma remains poorly understood. The lymphocyte to C-reactive protein ratio (LCR), a novel inflammatory-nutritional biomarker, has demonstrated predictive value in gastrointestinal cancers; however, its clinical relevance in cholangiocarcinoma has not been investigated.

Aim: To validate the LCR as an independent prognostic factor for overall survival (OS), surgical site infection (SSI), and length of hospital stay in patients with resectable cholangiocarcinoma.

Methods: We conducted a retrospective analysis of 76 patients with cholangiocarcinoma who underwent radical surgery between 2008 and 2013. The preoperative LCR was calculated as the lymphocyte count divided by C-reactive protein level, using a cutoff value of 180. Univariate and multivariate logistic regression analyses were performed to evaluate factors associated with SSI and hospitalization duration, while Kaplan-Meier survival curves and Cox proportional hazards models were used to assess predictors of OS.

Results: Patients in the low LCR group was significantly associated with several adverse clinical outcomes: A shorter median OS (14.93 months vs 46.67 months; P = 0.022); a 4.5-fold increased risk of prolonged hospitalization (P = 0.007); and a higher incidence of SSI (odds ratio = 4.41, P = 0.045). Multivariate analysis confirmed that LCR was an independent predictor of OS [hazard ratio (HR) = 3.204, P = 0.002], SSI, and hospitalization duration. Additionally, R0 resection (HR = 3.546, P = 0.002) and advanced tumor-node-metastasis stage (HR = 2.016, P = 0.035) were identified as independent prognostic factors for OS.

Conclusion: In this retrospective study, preoperative LCR is a cost-effective and practical biomarker that independently predicts OS, postoperative complications, and hospitalization duration in patients with resectable cholangiocarcinoma, thereby facilitating more precise patient stratification.

Background: Early recurrence is an important factor affecting the prognosis of hepatocellular carcinoma (HCC), but its preoperative prediction remains challenging.

Aim: To explore the value of a multimodal interpretable fusion model combining computed tomography (CT) habitat imaging (HI), radiomics, and clinical features in predicting early recurrence of HCC and analyze its correlation with pathological indicators.

Methods: The 191 HCC patients were categorized into early recurrence and non-early recurrence groups based on postoperative follow-up outcomes, and randomly divided into training and testing sets in a 7:3 ratio. Based on CT arterial phase and clinical data, the habitat model, radiomics model, clinical model, and fusion model were constructed and compared for their predictive ability in early recurrence of HCC. For the optimal model, SHapley Additive exPlanations (SHAP) analysis was performed to evaluate the contribution of different features in the model, and the correlation between HI and radiomics features with tumor microvascular invasion (MVI), Ki67 expression, GPC-3 expression, and pathological grading was analyzed.

Results: The fusion model demonstrated the best performance in predicting early recurrence of HCC, achieving the area under the curve of 0.933 on the validation set. The decision curve analysis curve indicated that the fusion model yielded the highest clinical net benefit. SHAP analysis provided valuable insights into explaining the fusion model's prediction of early HCC recurrence. Correlation analysis revealed significant associations between certain radiomics and Habitat features and pathological indicators such as MVI and Ki-67 expression in HCC.

Conclusion: An interpretable fusion model integrating clinical, radiomic, and habitat features can assist clinicians in identifying early postoperative recurrence of HCC, offering significant potential for prognosis prediction and clinical management.