Colorectal cancers (CRC) with KRAS mutations (KRASmut) are frequently included in consensus molecular subtype 3 (CMS3) with profound metabolic deregulation. We explored the transcriptomic impact of KRASmut, focusing on the tumor microenvironment (TME) and pathways beyond metabolic deregulation. The status of KRASmut in patients with CRC was investigated and overall survival (OS) was compared with wild-type KRAS (KRASwt). Next, we identified CMS, and further investigated differentially expressed genes (DEG) of KRASmut and distinctive pathways. Lastly, we used spatially resolved gene expression profiling to define the effect of KRASmut in the TME regions of CMS3-classified CRC tissues. CRC patients with KRASmut were mainly enriched in CMS3. Their specific enrichments of immune gene signatures in immunosuppressive TME were associated with worse OS. Activation of TGFβ signaling by KRASmut was related to reduced pro-inflammatory and cytokine gene signatures, leading to suppression of immune infiltration. Digital spatial profiling in TME regions of KRASmut CMS3-classified tissues suggested up-regulated genes, CD40, CTLA4, ARG1, STAT3, IDO, and CD274, that could be characteristic of immune suppression in TME. This study may help to depict the complex transcriptomic profile of KRASmut in immunosuppressive TME. Future studies and clinical trials in CRC patients with KRASmut should consider these transcriptional landscapes.
Stage 4 colon cancer (CC) presents a significant global health challenge due to its poor prognosis and limited treatment options. Tetraspanins, the transmembrane proteins involved in crucial cancer processes, have recently gained attention as diagnostic markers and therapeutic targets. However, their spatial expression and potential roles in stage 4 CC tissues remain unknown. Using the GeoMx digital spatial profiler, we profiled all 33 human tetraspanin genes in 48 areas within stage 4 CC tissues, segmented into immune, fibroblast, and tumor compartments. Our results unveiled diverse gene expression patterns across different primary tumor sub-regions. CD53 exhibited distinct overexpression in the immune compartment, hinting at a potential role in immune modulation. TSPAN9 was specifically overexpressed in the fibroblast compartment, suggesting involvement in tumor invasion and metastasis. CD9, CD151, TSPAN1, TSPAN3, TSPAN8, and TSPAN13 displayed specific overexpression in the tumor compartment, indicating potential roles in tumor growth. Furthermore, our differential analysis revealed significant spatial changes in tetraspanin expression between patient-matched stage 4 primary CC and metastatic liver tissues. These findings provide spatially resolved insights into the expression and potential roles of tetraspanins in stage 4 CC progression, proposing their utility as diagnostic markers and therapeutic targets. Understanding this landscape is beneficial for tailoring therapeutic strategies to specific sub-tumor regions in the context of stage 4 CC and liver metastasis.
In the highly contagious coronavirus disease 2019 pandemic, aerosol-generating procedures (AGPs) are associated with high-risk of transmission. Upper gastrointestinal endoscopy is a procedure with the potential to cause dissemination of bodily fluids. At present, there is no consensus that endoscopy is defined as an AGP. This review discusses the current evidence on this topic with additional management. Prevailing publications on coronavirus related to upper gastrointestinal endoscopy and aerosolization from the PubMed and Scopus databases were searched and reviewed. Comparative quantitative analyses showed a significant elevation of particle numbers, implying that aerosols were generated by upper gastrointestinal endoscopy. The associated source events have also been reported. To reduce the dispersion, certain protective measures have been developed. Endoscopic unit protocols are recommended for the concerned personnel. Therefore, upper gastrointestinal endoscopy should be classified as an AGP. Proper practices should be adopted by healthcare workers and patients.
Background/Aims: Achalasia is a rare esophageal motility disease, for which peroral endoscopic myotomy (POEM) has emerged as a promising treatment option; however, recurrence remains a challenge. Timed barium esophagography (TBE) is a useful diagnostic tool and potential outcome predictor of achalasia. This study aimed to determine predictive tools for recurrence after POEM.Methods: This retrospective study enrolled achalasia patients who underwent POEM between January 2015 and December 2021. Patients were categorized into two groups using the 1-month post-POEM Eckardt scores and TBE: the discordant group (Eckardt score improved >50%, TBE decreased 50%). Recurrence was defined as a reincrease in the Eckardt score to more than three during follow-up.Results: Complete medical records were available in 30 patients who underwent POEM. Seventeen patients (56.7%) were classified into the discordant group, while 13 patients (43.3%) were in the concordant group. The overall recurrence rate was 11.9% at 1-year, increasing to 23.8% during the extended follow-up. The discordant group had a 6.87 fold higher recurrence rate than the concordant group (52.9% vs. 7.7%, p=0.017).Conclusions: These results strongly suggest that combining the Eckardt score with TBE can effectively predict recurrent achalasia after POEM. Patients in the discordant group had an elevated risk.
Background/Aims: Achalasia is an esophageal motility disorder. Peroral endoscopic myotomy is widely used for all subtypes; however, randomized head-to-head evidence comparing the anterior and posterior approaches remains limited. We compared efficacy, safety, and reflux outcomes.Methods: We conducted a single-center, single-blind, prospective randomized controlled trial from February 2023 to August 2024. Twenty-eight patients with achalasia types I–III were randomized to anterior or posterior peroral endoscopic myotomy. The primary outcomes were esophageal acid exposure at 3 months (24-hour pH monitoring) and clinical success (Eckardt score ≤3). The secondary outcomes were procedural parameters, complications, timed barium esophagography, manometry, and reflux esophagitis.Results: Baseline characteristics were comparable between the groups. Procedural metrics and complication rates were similar and mild, with no severe adverse events. At 12 months, both groups showed significant symptom relief, reduced Eckardt scores, and decreased lower esophageal sphincter pressure. Posterior myotomy yielded a higher proportion of abnormal DeMeester scores (57.1% vs. 28.6%, p=0.14), although reflux esophagitis remained mild and comparable between the groups.Conclusions: Posterior peroral endoscopic myotomy demonstrated comparable efficacy, safety, and reflux outcomes. The anterior approach improved clearance on timed barium esophagography; however, both approaches achieved durable symptom control with acceptable safety profiles, supporting posterior myotomy as a valid alternative.