Journal of gastrointestinal oncology最新文献

{"title":"PRMT5 attenuates regorafenib-induced DNA damage in hepatocellular carcinoma cells through symmetric dimethylation of RPL14.","authors":"Wendi Bi, Xiaojuan Sun, Qiuyun Yi, Xinyu Jiang, Huisi He, Lixuan Jiang, Zhecai Fan, Hailing Huang, Wen Wen, Xiaoqing Jiang","doi":"10.21037/jgo-24-737","DOIUrl":"10.21037/jgo-24-737","url":null,"abstract":"<p><strong>Background: </strong>Regorafenib has been approved for second-line treatment of hepatocellular carcinoma (HCC) following sorafenib failure, but resistance to targeted therapy remains a major challenge. Enhancing the therapeutic sensitivity of HCC cells to regorafenib is crucial for improving treatment outcomes. This study aims to elucidate the role of PRMT5 in HCC and its impact on regorafenib sensitivity. Specifically, it focuses on the regulatory relationship between PRMT5 and RPL14, investigating their influence on DNA damage repair and drug resistance mechanisms in HCC.</p><p><strong>Methods: </strong>A stable PRMT5-overexpressing HCC cell line was constructed via lentiviral infection. Immunoprecipitation was employed to examine whether PRMT5 catalyzes the symmetric dimethylation of RPL14 at arginine residues. Western blot (WB) was used to assess changes in DNA damage markers (γ-H2AX) and DNA repair markers (RAD51) after RPL14 knockdown. Huh7 cells with PRMT5 overexpression, RPL14 knockdown, and combined PRMT5 overexpression and RPL14 knockdown were treated with regorafenib. DNA damage repair-related factors were analyzed using WB and immunofluorescence.</p><p><strong>Results: </strong>Mass spectrometry and immunoprecipitation confirmed the interaction between PRMT5 and RPL14, with PRMT5 catalyzing symmetric dimethylation of RPL14. RPL14 knockdown inhibited HCC cell proliferation, increased sensitivity to regorafenib, and disrupted DNA damage repair, while overexpression had the opposite effect. Regorafenib-treated PRMT5-overexpressing cells showed reduced γ-H2AX expression and improved survival, whereas RPL14 knockdown enhanced γ-H2AX levels and decreased survival. Notably, simultaneous PRMT5 overexpression and RPL14 knockdown significantly elevated γ-H2AX expression compared to PRMT5 overexpression alone, leading to reduced cell viability. These results suggest that PRMT5 modulates DNA damage repair through RPL14, influencing the sensitivity of HCC cells to regorafenib.</p><p><strong>Conclusions: </strong>PRMT5-mediated symmetric dimethylation of RPL14 stabilizes the protein, promoting DNA damage repair and contributing to regorafenib resistance in HCC. RPL14 plays a key role in PRMT5-driven enhancement of DNA damage repair and reduced drug sensitivity, identifying RPL14 as a potential therapeutic target to overcome regorafenib resistance in HCC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 1","pages":"191-208"},"PeriodicalIF":2.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geriatric Nutritional Risk Index is an effective prognostic predictor for metastatic/recurrent or unresectable esophageal cancer receiving immunotherapy.","authors":"Bei Wang, Zixuan Wang, Chuanhai Xu, Yueqin Wang, Honglan Gao, Haiping Liu, Mingyue Zheng, Zhenyuan Jiang, Zini Zhou, Gui Liu, Wei Geng","doi":"10.21037/jgo-24-722","DOIUrl":"10.21037/jgo-24-722","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have been extensively utilized in the treatment of esophageal squamous cell carcinoma (ESCC); however, patient responses to these therapies exhibit significant variability. This study aimed to investigate the prognostic value of Geriatric Nutritional Risk Index (GNRI) in patients with ESCC undergoing immunotherapy.</p><p><strong>Methods: </strong>A retrospective study was conducted on 677 patients with metastatic/recurrent or unresectable ESCC who received immunotherapy. Kaplan-Meier analysis and Log-rank test compared survival differences between high and low GNRI groups, while Cox proportional hazards models analyzed the impact of GNRI on survival in various subgroups and identified independent prognostic factors. Furthermore, immunohistochemistry (IHC) was performed on endoscopic biopsy tissues from 45 patients with unresectable disease who received immune ICIs as first-line treatments to investigate the predictive performance of GNRI combined with programmed cell death ligand 1 (PD-L1) for tumor response and overall survival (OS).</p><p><strong>Results: </strong>Regardless of metastatic/recurrent disease or unresectable status, patients with high GNRI levels had significantly longer OS time (P<0.001). Moreover, the protective role of GNRI was observed in various subgroups. Eastern Cooperative Oncology Group performance status (ECOG PS) score, distant organ metastasis, previous treatments, ICI modalities and GNRI were identified as independent prognostic factors for OS. Furthermore, the predictive performance of GNRI for OS may surpass that of PD-L1 expression (P=0.009 <i>vs.</i> P=0.38), while PD-L1 expression excelled in predicting tumor response (P=0.007 <i>vs.</i> P=0.08). The combination of these two indicators effectively predicted both tumor response (P=0.04) and OS (P=0.03) in immunotherapy.</p><p><strong>Conclusions: </strong>The GNRI serves as a robust prognostic indicator in patients with ESCC who are treated with ICIs. The integration of PD-L1 expression and GNRI demonstrates significant predictive value for tumor response and OS.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 1","pages":"1-16"},"PeriodicalIF":2.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a prognostic risk model for colorectal cancer and association of the prognostic model with cancer stem cell and immune cell infiltration.","authors":"Jian Zhang, Peter C Ambe, Aasma Shaukat","doi":"10.21037/jgo-2024-985","DOIUrl":"10.21037/jgo-2024-985","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The development of a prognostic model for patients with colorectal cancer (CRC) can facilitate the assessment of patient survival and the effectiveness of clinical treatments. A reasonable prognostic model can provide a basis for individualized treatment, prognostic risk stratification, and subsequent therapy for CRC patients. The aim of our study was to construct a prognostic model for patients with CRC using sequencing data derived from The Cancer Genome Atlas (TCGA) database.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Sequencing data of paracancerous tissues (n=51) and CRC samples (n=647) were downloaded from the TCGA database. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were employed to identify prognostic factors. A restricted cubic spline (RCS) model was used to assess the nonlinear relationship between risk score and poor overall survival (OS). The Genomics of Drug Sensitivity in Cancer (GDSC) database was accessed to evaluate the correlation between the prognostic model's risk score and drug sensitivity. The single-sample gene set enrichment analysis (ssGSEA), estimate, and CIBERSORT algorithms were applied to quantify the association between prognostic genes and immune cell infiltration in CRC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Our findings revealed that six genes, including Niemann-Pick C1-like 1 (&lt;i&gt;NPC1L1&lt;/i&gt;) [hazard ratio (HR) =1.53; 95% confidence interval (CI): 1.08-2.17; P=0.02], glucagon-like peptide 2 receptor (&lt;i&gt;GLP2R&lt;/i&gt;) (HR =0.68; 95% CI: 0.48-0.97; P=0.04), solute carrier family 8 member A3 (&lt;i&gt;SLC8A3&lt;/i&gt;) (HR =0.67; 95% CI: 0.47-0.96; P=0.03), alpha-1-microglobulin/bikunin precursor (&lt;i&gt;AMBP&lt;/i&gt;) (HR =0.64; 95% CI: 0.45-0.91; P=0.01), single-pass membrane protein with coiled-coil domains 2 (&lt;i&gt;SMCO2&lt;/i&gt;) (HR =0.68; 95% CI: 0.48-0.97; P=0.03), and tetratricopeptide repeat domain 16 (&lt;i&gt;TTC16&lt;/i&gt;) (HR =1.55; 95% CI: 1.09-2.20; P=0.02) function as independent prognostic factors for CRC. Based on these six genes, the developed prognostic assessment model identified a strong association between high risk score and poor OS (HR =2.43; 95% CI: 1.67-3.53; P&lt;0.001) in patients with CRC. Furthermore, the analysis revealed a nonlinear relationship (P&lt;0.001) between continuous variation in risk score and the risk of poor OS. Additionally, specific genes included in the prognostic model were found to be strongly associated with cancer stem cell and immune cell infiltration in CRC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;We developed a prognostic risk model incorporating a six-gene panel for patients with CRC. Our analysis revealed a nonlinear relationship between this prognostic model and OS in patients with CRC. A high risk score was associated with poor prognosis, indicating that the adverse outcomes observed in patients with CRC may be influenced by cancer stem cell and immune cell infiltration. Our model provides a promising predictive method for the prognosis of CRC patients,","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 1","pages":"77-91"},"PeriodicalIF":2.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver microsomal protein content and activity in patients with hepatocellular carcinoma and cirrhosis: implications for the <i>in vivo</i> prediction of individual hepatic clearance.","authors":"Jun Zhou, Na Gao, Xin Tian, Yan Fang, Jie Gao, Qiang Wen, Ming-Zhu Cui, Yun-Fei Zhang, Sai-Fei Li, Lin-Jing Jia, Hai-Ling Qiao","doi":"10.21037/jgo-2024-963","DOIUrl":"10.21037/jgo-2024-963","url":null,"abstract":"<p><strong>Background: </strong>The hepatic metabolism of patients with hepatocellular carcinoma and cirrhosis (HCCC) may differ from that of patients with hepatocellular carcinoma (HCC) without cirrhosis, limiting the clinical individualized dosing regimens for these patients. Microsomal protein per gram of liver (MPPGL) is an important scaling factor for physiologically based pharmacokinetic models, but data in patients with HCCC are limited. The study aims to determine the content of MPPGL in patients with HCCC and to guide individualized clinical dosing of patients with HCCC using <i>in vitro</i> drug metabolism data.</p><p><strong>Methods: </strong>The microsomal protein content was determined in liver samples of patients with HCCC (n=48) and in normal liver samples (n=68). The activity of 10 cytochrome P450 (CYP) isoforms at the microsomal protein level (CL_M) was determined. According to the value of MPPGL and CL_M, the activity of CYPs in the liver tissue clearance (CL_L) and predicted <i>in vivo</i> hepatic clearance (CL_H) were extrapolated.</p><p><strong>Results: </strong>The median value of MPPGL was significantly lower in patients with HCCC (28.35 mg/g) than in the controls (37.65 mg/g) (P=0.008). In patients with HCCC as compared to controls, the CL_M of CYP1A2, CYP2C8, and CYP2C19 was significantly decreased while that of CYP2D6 and CYP2E1 was significantly increased; meanwhile, the CL_M of CYP2A6, CYP2B6, CYP2C9, and CYP3A4/5 was not significantly changed. The changes in CL_L were not consistent with those in CL_M among patients with HCCC. The median spearman rank correlation coefficient was 0.7880±0.079 between CL_H and CL_M and was 0.9868±0.022 between CL_H and CL_L for the 10 CYPs (P<0.001).</p><p><strong>Conclusions: </strong>In patients with HCCC, MPPGL content was significantly reduced, and a variable change in the activity of 10 CYP was observed in microsomes. When taking individual MPPGL into account, CL_L is better suited than CL_M to represent the <i>in vitro</i> metabolism of CYPs, with the strongest correlation being observed between CL_L and <i>in vivo</i> CL_H. This finding holds potential value for guiding clinical management of drugs in patients with HCCC.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 1","pages":"146-158"},"PeriodicalIF":2.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to anti-EGFR therapy in chemo-refractory right-sided RAS wild-type metastatic colorectal cancer: a case report and literature review.","authors":"Annie Xiao, Marwan Fakih","doi":"10.21037/jgo-24-458","DOIUrl":"10.21037/jgo-24-458","url":null,"abstract":"<p><strong>Background: </strong>Anti-epidermal growth factor receptor (EGFR) therapies are important targeted agents in the treatment of metastatic colorectal cancer (CRC). However, clinical benefit is limited to patients with left-sided primary tumors and RAS wild-type (WT) disease. In right-sided chemo-refractory settings, response to anti-EGFR therapy has not been reported to date.</p><p><strong>Case description: </strong>We present a case of a 70-year-old man with metachronous metastatic ascending colon adenocarcinoma who experienced an exceptional response to FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus panitumumab after failing multiple lines of therapy. He was initially diagnosed with stage IIIB (pT4aN1M0) disease and underwent hemicolectomy followed by adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin). Nine months after completion of adjuvant therapy, disease recurred in the liver, peritoneum, and mesenteric lymph nodes. Subsequent treatments included FOLFIRI plus bevacizumab and FOLFOX with eventual progression. Tumor genomic profiling revealed RAS/RAF WT disease, and in the absence of anti-EGFR therapy resistance mutations, the patient was offered treatment with FOLFIRI plus panitumumab. He achieved immediate palliation of his abdominal pain after one cycle, followed by normalization of his tumor markers and significant tumor regression of his hepatic, peritoneal, lung, and distant lymph node metastases within four cycles.</p><p><strong>Conclusions: </strong>Treatment options for right-sided RAS-WT metastatic CRC are limited, particularly after progression on standard chemotherapies. While anti-EGFR antibodies have demonstrated detrimental survival impact in the first-line setting for right-sided CRC, their performance in later lines is less well-characterized. This case challenges the notion of right-sided disease as uniformly resistant to EGFR inhibition and highlights the need for additional biomarker studies to identify the subset of right-sided CRC that may benefit from EGFR targeted strategies. Emerging evidence suggests that more stringent genomic criteria for EGFR resistance, beyond RAS mutation status alone, may refine patient selection for benefit from anti-EGFR therapies.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 1","pages":"292-300"},"PeriodicalIF":2.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Budding\"-an early MRI feature established in a case-control study of perianal fistula mucinous adenocarcinoma.","authors":"Lillian Reza, Alison Corr, Philip Tozer, John T Jenkins, Anthony Antoniou, Elaine M Burns, David Burling, Ailsa Hart, Sue K Clark, Phillip Lung","doi":"10.21037/jgo-24-562","DOIUrl":"10.21037/jgo-24-562","url":null,"abstract":"<p><strong>Background: </strong>Perianal fistula mucinous adenocarcinoma (FMA) usually presents at an advanced stage, necessitating extensive surgical resection. Symptoms of perianal pain and discharge are indistinguishable from fistula sepsis. Absence of defined features on magnetic resonance imaging (MRI) precludes early diagnosis. This study aims to validate MRI features that should increase suspicion of early mucinous transformation, prompting urgent examination and targeted biopsies.</p><p><strong>Methods: </strong>Retrospective review of MRI studies was conducted in 9 patients with FMA in Crohn's perianal and non-Crohn's ileoanal pouch fistula between 2015-2019. Radiological features were assessed. Fine T2-weighted high signal lobulation of the fistula tract on MRI, described as 'budding', was retrospectively noted on historic studies in all cases of FMA and was determined a feature distinct from expected T2-weighted high signal appearance of bland fistula sepsis. The significance of these features in early diagnosis of FMA was assessed using a case control study.</p><p><strong>Results: </strong>'Budding', mass-like expansion of the tract, and septation of T2-weighted high signal components of the fistula were significantly associated with FMA using Fisher's exact test (P<0.001). The presence of T2-weighted high signal \"budding\" predated the histological confirmation of FMA by a median 36 months (range, 12-156 months). One control patient was diagnosed with FMA during the study as 'budding' was retrospectively detected, triggering urgent targeted biopsy.</p><p><strong>Conclusions: </strong>Radiological awareness of early features of FMA may improve outcomes by reducing the morbidity of exenterative surgery with delayed diagnosis. The presence of T2-weighted high signal 'budding' on MRI should prompt urgent targeted biopsy.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 1","pages":"106-114"},"PeriodicalIF":2.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The combination of extra-Glissonian pedicle ligation of the tumor-bearing area and traditional ALPPS: a novel modified ALPPS method.","authors":"Zhu Chen, Xingyu Chen, Haiyang Hu, Kai Chen, Heng Xiao, Chengyou Du, Xiang Lan","doi":"10.21037/jgo-24-691","DOIUrl":"10.21037/jgo-24-691","url":null,"abstract":"<p><p>Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can provide patients with large liver tumors the opportunity to undergo radical resection. However, tumor progression between the surgical stages and unsatisfactory hyperplasia of the residual liver reduces the second-stage resection rate and limit the application of ALPPS. We reported a novel modified ALPPS method that can accelerate tumor necrosis and hyperplasia of the residual liver and increase the second-stage resection rate. The data of patients who underwent the novel modified ALPPS procedure in our hospital between September 2021 and April 2024 were retrospectively analyzed. In addition to ligation of the right hepatic portal vein and liver partition during the first stage, we transected all the Glissonian pedicles of the tumor-bearing area to accelerate tumor necrosis. Ultimately, three patients underwent this novel modified ALPPS procedure. Second-stage resection was successfully performed in all these patients. Satisfactory hyperplasia was obtained in the residual liver before the second stage of surgery. The tumor-bearing area showed obvious necrosis and atrophy. The residual liver volumes of the three patients increased by 83%, 23%, and 49%, respectively. No postoperative complications or tumor recurrence was observed. This novel modified approach is safe and effective. This approach can prevent tumor progression between the surgical stages and promote compensatory liver proliferation.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 1","pages":"317-326"},"PeriodicalIF":2.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel nebulized drug delivery system based on an innovative high-pressure peristaltic pump availably applied to pressurized intraperitoneal aerosol chemotherapy.","authors":"Renjie Li, Qiming Fan, Xiaosong Lin, Ruijian Chen, Bingcong Luo, Zifeng Yang, Yong Li","doi":"10.21037/jgo-2024-1009","DOIUrl":"10.21037/jgo-2024-1009","url":null,"abstract":"<p><strong>Background: </strong>Management of peritoneal carcinomatosis (PC) remains a significant clinical challenge due to a lack of effective therapies. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been identified as a safe and efficacious treatment for PC. However, despite the observed high potential for PIPAC in treating numerous PC cases, the technology is still limited in China. To address this deficit, we developed a novel nebulized drug delivery system (NDDS) and evaluated it in this study.</p><p><strong>Methods: </strong>The NDDS was developed and was systematically assessed through tests of mechanical properties, granulometric analyses, sprayed distribution tests, and gravimetric analyses; moreover, drug penetration and distribution were examined <i>in vitro</i> and in a porcine model (female Tibetan pig).</p><p><strong>Results: </strong>The NDDS, which included a high-pressure peristaltic pump, demonstrated a pressure initiation time of 5 s and a spray angle of 70°. Nebulization was consistent from the fifth second onward, with a median droplet diameter of 25.0-26.5 µm. The diameters of the sprayed intensive and expanded area were 26.1±1.4 and 48.5±1.0 cm at the vertical distance of 15 cm, and the stress generated was ≤3.790 Pa. Intraluminal drug distribution was extensive but heterogeneity, with 100- to 400-µm drug penetration depth (PD), and the optimal drug PD was observed in locations directly opposite to or adjacent surrounding the nozzle.</p><p><strong>Conclusions: </strong>The developed NDDS demonstrated promising mechanical properties, effective granulometric characteristics, extensive spray coverage, and satisfactory drug penetration and distribution. It offers a practicable solution for the application of PIPAC and will hopefully improve the current dilemma in PC therapy.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 1","pages":"234-248"},"PeriodicalIF":2.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world effectiveness and safety of TACE combined with lenvatinib plus immune checkpoint inhibitors in patients with BCLC-B stage hepatocellular carcinoma.","authors":"Yu Yao, Xiang Nong, Jing-Chang Liang, Yu-Mei Zhang, Zhi-Ming Zhang","doi":"10.21037/jgo-2025-33","DOIUrl":"10.21037/jgo-2025-33","url":null,"abstract":"<p><strong>Background: </strong>More effective treatment strategies need to be established for patients with Barcelona Clinic Liver Cancer (BCLC)-B stage hepatocellular carcinoma (HCC). The combination of transarterial chemoembolization (TACE) with lenvatinib and immune checkpoint inhibitors (ICIs) has been shown to have potential in the treatment of unresectable HCC. However, the real-world data on the use of this combined therapy in patients with BCLC-B stage HCC are limited. Therefore, this study aimed to validate the efficacy and safety of the combination of TACE with lenvatinib plus ICIs in the treatment of patients with BCLC-B stage HCC in a real-world setting.</p><p><strong>Methods: </strong>A total of 121 patients who were newly diagnosed with BCLC-B stage HCC were enrolled in this study. Of these patients, 52 received treatment with TACE combined with lenvatinib plus ICIs (the combination group), and 69 received TACE alone (the monotherapy group). Propensity score matching (PSM) was used to reduce potential biases. The primary endpoint of the study was overall survival (OS), while the secondary endpoints were progression-free survival (PFS), the objective response rate (ORR), and the disease control rate (DCR). Adverse events (AEs) were also recorded and evaluated.</p><p><strong>Results: </strong>The OS of the combination group was longer than that of the monotherapy group (median OS: 30.9 <i>vs</i>. 13.0 months, P<0.001), as was the PFS (median PFS: 12.3 <i>vs</i>. 8.3 months, P=0.19). The ORR of the combination group was higher than that of the monotherapy group (61.5% <i>vs</i>. 33.3%, P=0.002), as was the DCR (92.3% <i>vs</i>. 76.8%, P=0.02). After PSM, the OS of the combination group was longer than that of the monotherapy group (median OS: not reached <i>vs</i>. 9.8 months, P<0.001), as was the PFS (median PFS: 13.4 <i>vs</i>. 7.6 months, P=0.28). The ORR of the combination group was higher than that of the monotherapy group (59.0% <i>vs</i>. 30.8%, P=0.01), as was the DCR (89.7% <i>vs</i>. 74.4%, P=0.08). In the multivariate Cox regression analysis, combination therapy was associated with a better OS (hazard ratio =0.36, 95% confidence interval: 0.20-0.64, P<0.001). In terms of the AEs, 8 of 52 patients (15.4%) in the combination group, and 4 of 69 patients (5.8%) in the monotherapy group experienced grade 3 or 4 AEs (P=0.08), but no grade 5 AEs were observed.</p><p><strong>Conclusions: </strong>The combination of TACE with lenvatinib plus ICIs showed excellent efficacy in the treatment of patients with BCLC-B stage HCC, and the safety profile was acceptable.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 1","pages":"176-190"},"PeriodicalIF":2.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence algorithm was used to establish and verify the prediction model of portal hypertension in hepatocellular carcinoma based on clinical parameters and imaging features.","authors":"Yongfei He, Qiang Gao, Shutian Mo, Ketuan Huang, Yuan Liao, Tianyi Liang, Meifeng Chen, Jicai Wang, Qiang Tao, Guangquan Zhang, Fenfang Wu, Chuangye Han, Xianjie Shi, Tao Peng","doi":"10.21037/jgo-2024-931","DOIUrl":"10.21037/jgo-2024-931","url":null,"abstract":"<p><strong>Background: </strong>Portal hypertension (PHT) is an important factor leading to a poor prognosis in patients with hepatocellular carcinoma (HCC). Identifying patients with PHT for individualized treatment is of great clinical significance. The prediction model of HCC combined PHT is in urgent need of clinical practice. Combining clinical parameters and imaging features can improve prediction accuracy. The application of artificial intelligence algorithms can further tap the potential of data, optimize the prediction model, and provide strong support for early intervention and personalized treatment of PHT. This study aimed to establish a prediction model of PHT based on the clinicopathological features of PHT and computed tomography scanning features of the non-tumor liver area in the portal vein stage.</p><p><strong>Methods: </strong>A total of 884 patients were enrolled in this study, and randomly divided into a training set of 707 patients (of whom 89 had PHT) and a validation set of 177 patients (of whom 23 had PHT) at a ratio of 8:2. Univariate and multivariate logistic regression analyses were performed to screen the clinical features. Radiomics and deep-learning features were extracted from the non-tumorous liver regions. Feature selection was conducted using <i>t</i>-tests, correlation analyses, and least absolute shrinkage and selection operator regression models. Finally, a predictive model for PHT in HCC patients was constructed by combining clinical features with the selected radiomics and deep-learning features.</p><p><strong>Results: </strong>Portal vein diameter (PVD), Child-Pugh score, and fibrosis 4 (FIB-4) score were identified as independent risk factors for PHT. The predictive model that incorporated clinical features, radiomics features from non-tumorous liver regions, and deep-learning features had an area under the curve (AUC) of 0.966 [95% confidence interval (CI): 0.954-0.979] and a sensitivity of 0.966 in the training set, and an AUC of 0.698 (95% CI: 0.565-0.831) and a sensitivity of 0.609 in the validation set.</p><p><strong>Conclusions: </strong>The preoperative evaluation showed that increased PVD, higher Child-Pugh score, and increased FIB-4 score were independent risk factors for PHT in patients with HCC. To predict the occurrence of PHT more effectively, we construct a comprehensive prediction model. The model incorporates clinical parameters, radiomic features, and deep learning features. This fusion of multi-modal features enables the model to capture complex information related to PHT more comprehensively, thus achieving high prediction accuracy and practicability.</p>","PeriodicalId":15841,"journal":{"name":"Journal of gastrointestinal oncology","volume":"16 1","pages":"159-175"},"PeriodicalIF":2.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}