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Background: CT-detected Extramural venous invasion (EMVI) is known as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). However, the molecular basis is not clear. In colorectal cancer, M2 macrophages plays a vital role in determining EMVI. This study aimed to investigate the relationship between CT-detected EMVI and the M2 macrophages as well as prognosis predictionusing a radiogenomic approach. Method: We utilized EMVI-related genes (from mRNA sequencing of 13 GC samples correlated with EMVI score by spearman analysis, P < 0.01) to overlap the co-expression genes of WGCNA module and M2 macrophages related genes (from mRNA data of 371 GC patients in TCGA database), generating a total of 136 genes. An EMVI-M2-prognosis-related hub gene signature was constructed by COX and least absolute shrinkage and selection operator (LASSO) analysis from a training cohort TCGA database (n = 371) and validated it in a validation cohort from GEO database (n = 357). High- and low-risk groups were divided by hub gene (EGFLAM and GNG11) signature-derived risk scores. We assessed its predictive ability through Kaplan-Meier (K-M) curve and COX analysis. Furthermore, we utilized ESTIMATE to detect tumor mutation burden (TMB) and evaluate sensitivity to immune checkpoint inhibitors (ICIs). Expression of hub genes was tested using western blotting and immunohistochemistry (IHC) analysis. Results: The overall survival (OS) was significantly reduced in the high-risk group (Training/Validation: AUC = 0.701/0.620; P < 0.001/0.003). Furthermore, the risk score was identified as an independent predictor of OS in multivariate COX regression analyses (Training/Validation: HR = 1.909/1.928; 95% CI: 1.225–2.974/1.308–2.844). The low-risk group exhibited significantly higher TMB levels (P = 1.6e− 07) and greater sensitivity to ICIs. Significant higher expression of hub-genes was identified on multiple GC cell lines and original samples. Hub-genes knockdown in gastric cancer cell lines inhibited their proliferation, metastatic and invasive capacity to varying degrees. In vivo experiments indicate that EGFLAM, as one of the hub genes, its high expression can serve as a biomarker for low response to immunotherapy. Conclusion: Our study demonstrated EMVI-M2 gene signature could effectively predict the prognosis of GC tissue, reflecting the relationship between EMVI and M2 macrophages. [ABSTRACT FROM AUTHOR]

Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361) [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer (GC) is a severe disease with high mortality. There is an immediate demand for GC prognostic markers. The biological role of the lethal (3) malignant brain tumor-like 3 (L3MBTL3) has been investigated in human malignancies, but its involvement in GC is not well understood. This research seeks to better understand L3MBTL3's prognostic significance and expression profiles in GC. We examined the expression and prognostic significance of L3MBTL3 in GC using bioinformatic analysis. A functional enrichment analysis was conducted to explore the potential mechanisms. The correlations between L3MBTL3 and immune infiltration were determined based on the TIMER database. Our work revealed that L3MBTL3 is a promising diagnostic and prognostic marker for GC, opening new avenues for research and treatment. Recent research has linked lethal (3) malignant brain tumor-like 3 (L3MBTL3) to cancer aggressiveness and a dismal prognosis, but its function in gastric cancer (GC) is unclear. This research investigated the association between L3MBTL3 expression and clinicopathological characteristics of GC cases, as well as its prognostic value and biological function based on large-scale databases and clinical samples. The results showed that L3MBTL3 expression was upregulated in malignant GC tissues, which was associated with a shortened survival time and poor clinicopathological characteristics, including TNM staging. A functional enrichment analysis including GO/KEGG and GSEA illustrated the enrichment of different L3MBTL3-associated pathways involved in carcinogenesis and immune response. In addition, the correlations between L3MBTL3 and tumor-infiltrating immune cells were determined based on the TIMER database; the results showed that L3MBTL3 was associated with the immune infiltration of macrophages and their polarization from M1 to M2. Furthermore, our findings suggested a possible function for L3MBTL3 in the regulation of the tumor immune microenvironment of GC. In summary, L3MBTL3 has diagnostic potential, and it also offers new insights into the development of aggressiveness and prognosis in GC. [ABSTRACT FROM AUTHOR]

Fournier's gangrene (FG) is an extremely rare necrotizing fasciitis that is insidious, rapidly spreading and life-threatening. FGs due to rectal cancer occur rarely and there is a lack of clinical reference. In the present study, a severe FG due to rectal cancer perforation was described and the features of this rare disease were summarized with a literature review. A 57-year-old man was admitted because of rectal cancer-induced FG. The patient was misdiagnosed with extensive perianal abscess until the intraoperative biopsy confirmed that rectal cancer was the culprit. Incision, debridement and drainage were carried out to reduce infectious burdens. After that, the patient was transferred to Peking University People's Hospital for the subsequent therapy. Empirical broad-spectrum antibiotic therapy was used at the initial stage. Diversional transverse loop colostomy was performed to control infection and resume oral feeding. After four rounds of vacuum-assisted closure (VAC) therapy, radical resection and wound closure were accomplished. The scrotal defect was repaired by a skin flap. Pathological results indicated a moderately differentiated adenocarcinoma with perforation. The patient was discharged from the hospital on postoperative day 15 without any post-operative complications. No signs of recurrence were observed during a 22-month follow-up. In the setting of rectal cancer-induced FGs, the liquid resuscitation, broad-spectrum antibiotic therapy, and prompt debridement are the cornerstones of the initial management. Diversional colostomy and VAC therapy were effective in the management of severe infection and large wounds. The present case report also provided a clinical reference for the implementation of staged surgeries and the perioperative multidisciplinary management of FGs. [ABSTRACT FROM AUTHOR]

Purpose: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME., Methods: This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS)., Results: Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group)., Conclusion: This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.

Background: Tumor cell inhibition is a pivotal focus in anti-cancer research, and extensive investigations have been conducted regarding the role of p53 . Numerous studies have highlighted its close association with reactive oxygen species (ROS). However, the precise impact of the antioxidant glutathione (GSH) in this context remains inadequately elucidated. Here, we will elucidate the anti-cancer mechanisms mediated by p53 following treatment with GSH., Methods: In this study, we employed a p53 gene knockout approach in SW480 colorectal cells and conducted comprehensive analyses of 20 amino acids and proteomics using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS)., Results: These analyses unveiled profound alterations in amino acids and proteins triggered by GSH treatment, shedding light on novel phenomena and delineating the intricate interplay between GSH and cellular proteins. The deletion of the p53 gene exerts a profound influence on tumor cell proliferation. Moreover, tumor cell proliferation is significantly affected by elevated GSH levels. Importantly, in the absence of the p53 gene, cells exhibit heightened sensitivity to GSH, leading to inhibited cell growth. The combined therapeutic approach involving GSH and p53 gene deletion expedites the demise of tumor cells. It is noteworthy that this treatment leads to a marked decline in amino acid metabolism, particularly affecting the down-regulation of methionine (Met) and phenylalanine (Phe) amino acids. Among the 41 proteins displaying significant changes, 8 exhibit consistent alterations, with 5 experiencing decreased levels and 3 demonstrating increased quantities. These proteins primarily participate in crucial cellular metabolic processes and immune functions., Conclusions: In conclusion, the concurrent administration of GSH treatment and p53 gene deletion triggers substantial modifications in the amino acid and protein metabolism of tumor cells, primarily characterized by down-regulation. This, in turn, compromises cell metabolic activity and immune function, ultimately culminating in the demise of tumor cells. These newfound insights hold promising implications and could pave the way for the development of straightforward and efficacious anti-cancer treatments., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-236/coif). The authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Improving cancer therapy by targeting the adverse tumor microenvironment (TME) rather than the cancer cells presents a novel and potentially effective strategy. In this study, we introduced Fe x Mo y S nanoparticles (NPs), which act as sequential bioreactors to manipulate the TME. Fe x Mo y S NPs were synthesized using thermal decomposition and modified with polyethylene glycol (PEG). Their morphology, chemical composition, and photothermal properties were characterized. The capability to produce ROS and deplete GSH was evaluated. Effects on CRC cells, including cell viability, apoptosis, and glycolysis, were tested through various in vitro assays. In vivo efficacy was determined using CRC-bearing mouse models and patient-derived xenograft (PDX) models. The impact on the MAPK signaling pathway and tumor metabolism was also examined. The Fe x Mo y S NPs showed efficient catalytic activity, leading to increased ROS production and GSH depletion, inducing ferroptosis, and suppressing glycolysis in CRC cells. In vivo, the NPs significantly inhibited tumor growth, particularly when combined with NIR light therapy, indicating a synergistic effect of photothermal therapy and chemodynamic therapy. Biosafety assessments revealed no significant toxicity in treated mice. RNA sequencing suggested that the NPs impact metabolism and potentially immune processes within CRC cells. Fe x Mo y S NPs present a promising multifaceted approach for CRC treatment, effectively targeting tumor cells while maintaining biosafety. The nanoparticles exhibit potential for clinical translation, offering a new avenue for cancer therapy., (© 2024. The Author(s).)

Introduction: In recent years, the incidence of thyroid cancer has increased manyfold and young adults, who have a greater financial burden and occupational stress, comprise a large number. Previous studies have shown mixed results, even distinct results, on suicide rates among thyroid cancer survivors. As the overdiagnosis and overtreatment of thyroid cancer has gradually become a topical issue, the study aims to summarise the risk of suicide among patients with thyroid cancer to provide robust evidence of the effects of thyroid cancer on suicide., Methods and Analysis: A total of six databases (MEDLINE, Embase, Web of Science Core Collection, PsycINFO, CINAHL and Google Scholar) will be searched according to MeSH, subheadings, and free words, and the planned search date is 31 Jnauary 2024. The search strategy had three parts, such as suicide, cancer and epidemiological studies, moreover, we will collect the detailed suicide information by reviewers' extraction. Standard mortality ratio (SMR) was used as the outcome measure, when SMRs were not available, the risk ratio, HR and detailed number of suicides were extracted to calculate the SMRs., Ethics and Dissemination: The Institutional Review Board of Peking University People's Hospital provided ethical approval exemption and approved the data collection and subsequent analyses in accordance with the Declaration of Helsinki as revised in 2013., Prospero Registration Number: CRD42023445542., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)