Vitoon Chinswangwatanakul

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.

Esophageal cancer is frequently diagnosed at an advanced stage, limiting opportunities for curative treatment and contributing to poor clinical outcomes. We aimed to identify clinicopathological predictors of advanced-stage presentation and use these findings to inform a registry-informed framework for earlier detection of esophageal adenocarcinoma (AC) in Thailand. A retrospective cohort study was conducted using the Siriraj Cancer Registry. Among 1451 patients diagnosed with esophageal cancer between 2009 and 2024, 591 patients with sufficient clinical and/or pathological information for stage assignment were included. Patients were classified as having early-stage (Stage I–II) or advanced-stage (Stage III–IV) disease. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of advanced-stage presentation. Among patients with sufficient information for reliable stage assignment, 77.5% presented with advanced-stage disease. AC histology was independently associated with increased odds of advanced-stage presentation compared with squamous cell carcinoma (adjusted odds ratio 4.16, 95% confidence interval 1.21–14.30; p = 0.024). A trend toward earlier-stage diagnosis was observed during 2017–2024 compared with 2009–2016 (adjusted odds ratio 0.66, 95% confidence interval 0.43–1.00; p = 0.052). These findings provide hypothesis-generating evidence to inform a risk-based approach to earlier evaluation of individuals at increased risk of esophageal AC in Thailand, which requires prospective validation.

Chatbadin Thongchuam, Chainarong Phalanusitthepha, Vitoon Chinswangwatanakul, Thawatchai Akaraviputh, Asada Methasate, Jirawat Swangsri, Tharathorn Suwatthanarak. Journal of Minimally Invasive Surgery 2026;29:158-62. https://doi.org/10.7602/jmis.2026.29.3.158

Objective: To identify gene-expression features associated with lymph node metastasis (LNM) in colorectal cancer (CRC) and to develop a transcriptomic-clinical predictive model for preoperative nodal assessment. Materials and Methods: A total of 151 CRC tissue samples (74 LNM– and 77 LNM+) were analyzed using RNA sequencing. Differentially expressed genes (DEGs) were identified with DESeq2, and functional enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). A Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression model integrating gene-expression features with clinical variables was developed to predict LNM status. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results: A total of 302 DEGs were identified in LNM+ CRC, including 178 upregulated and 124 downregulated genes. Upregulated genes were enriched in chemokine-mediated signaling, epithelial morphogenesis, and intermediate filament organization, whereas downregulated genes were associated with adaptive immune response and complement activation. In multivariate analysis, lymphovascular invasion (LVI) was the only clinical variable independently associated with LNM. The optimized LASSO model, combining LVI with selected transcriptomic features demonstrated excellent discriminatory performance (AUC ≈ 0.92). Key upregulated genes included CCL21, CCL26, DEFB1, LST1, KANK4, TNNC1, PFDN6, TENM1, CST6, and PADI3, while IGHV2-26 was downregulated. Conclusion: Integration of LVI with transcriptomic signatures enables accurate prediction of lymph node metastasis in CRC and supports biopsy-based risk assessment to guide clinical decision-making.

Colorectal cancer (CRC) exhibits marked genomic and immune heterogeneity; stage III CRC remains prone to recurrence and metastasis despite standard therapy. To delineate genotype–immune relationships, we integrated whole-exome sequencing and transcriptomic profiling in 69 Thai patients with stage III CRC. We investigated the top 3 somatic mutations and their effects on the tumor immune microenvironment. Our analysis identified TP53 , APC , and KRAS as the most frequently mutated genes, each associated with distinct immune phenotypes. We observed a clear dichotomy: APC and TP53 mutations correlated with an immune-depleted, exclusionary phenotype, whereas activating KRAS mutations were linked to a pro-inflammatory, myeloid-rich microenvironment. In tumors harboring co-mutations, the KRAS -associated inflammatory signature predominated and correlated with a trend toward poorer overall survival (hazard ratio = 17.4, 95% CI: 1.8–170.8, P = 0.014). KRAS co-occurrence with TP53 retained the inflammatory signature and similarly correlated with a trend toward poorer overall survival (hazard ratio = 10.6, 95% CI: 1.2–91.2, P = 0.032). These findings indicate that CRC evolution establishes predictable, genotype-specific immune archetypes that distinguish immune-depleted from dysfunctional inflamed tumors. This framework may serve as a biomarker to stratify patients and guide tailored immunotherapy strategies for stage III CRC.

Early detection of gastrointestinal (GI) cancers—including colorectal cancer (CRC), gastric cancer (GC), and esophagogastric junction cancer (EGJC)—is essential for improving patient outcomes. However, current diagnostic methods such as endoscopy and colonoscopy are invasive, costly, and not widely accessible. Proteases are elevated in many cancers and are detectable in peripheral blood, making them promising candidates for noninvasive diagnostic strategies. We employed a six-probe charge-changing peptide (CCP) panel to profile cancer-associated protease activity in human plasma. Each CCP undergoes a charge shift upon cleavage by a specific protease, enabling detection via gel electrophoresis. Plasma samples from GI cancer patients (CRC, GC, EGJC; N = 68) and healthy controls (HC; N = 31) were analyzed. Protease activity profiles were analyzed using statistical tests, principal component analysis, and binary logistic regression (LR) models trained on the most informative probes. Model performance was evaluated through repeated cross-validation. Distinct protease activity profiles were observed among CRC, upper GI cancers (UGIC; GC + EGJC), and HC groups. Probe designed to be cleaved by cathepsin B showed the strongest discrimination between cancer and control samples, while probes designed to be cleaved by ubiquitin-specific peptidase 15 and plasmin were identified as the most informative subtype-specific markers for UGIC and CRC, respectively. LR models built on these single probes demonstrated excellent diagnostic performance, with AUCs exceeding 0.95, and both sensitivity and specificity greater than 90%. Our findings highlight CCP-based protease profiling as a minimally invasive, accurate, and scalable method for GI cancer detection and classification. This platform holds strong potential for clinical application in cancer screening, pending further validation in larger, independent cohorts.

Objective: This study compared immune transcriptome profiles between SCC patients achieving cCR and those with incomplete responses to CRT using the NanoString Ncounter® Pancancer Immune Profiling Panel. Materials and Methods: A retrospective cohort of 36 SCC patients treated with CRT was analyzed. Clinical data and blood samples were collected, and immune transcriptome profiling was conducted. Differential gene expression analysis identified distinctions between cCR and non-clinical complete response (non-cCR) groups. Results: Of the 36 patients, 20 achieved cCR, while 16 had nonc-CR. Significant differences in immune transcriptomes were observed, particularly in IL-12 signaling mediated by STAT4. In the cCR group, 72 genes were upregulated, and 13 were downregulated, suggesting their role as predictive biomarkers for treatment response. Conclusions: This study identified distinct immune transcriptome profiles in SCC patients with cCR versus non-cCR, highlighting genes related to IL-12 signaling as potential biomarkers. These findings emphasize the role of immune-related gene expression in determining patient outcomes and may support personalized therapeutic strategies to enhance CRT efficacy in SCC patients.

Understanding the metastatic cascade is critical for the treatment and prevention of cancer-related death. Within a tumor, immune cells have the capacity to fuse with tumor cells to generate tumor-immune hybrid cells (THCs). THCs are hypothesized to be a subset of cancer cells with the capacity to enter circulation as circulating hybrid cells (CHC) and seed metastases. To understand the mechanism of THC metastasis, we investigated CHCs in peripheral blood from patients with stage IV colorectal cancer (CRC), as well as THCs in tissues of primary colorectal cancers and their liver metastasis sites using immunofluorescence, spatial proteomic, spatial transcriptomic, molecular classification, and molecular pathway analyses. Our findings indicated a high prevalence of CHCs and THCs in patients with stage IV CRC. THCs expressed CTLA4 in primary CRC lesions and correlated with upregulation of CD68, CD4, and HLA-DR in metastatic liver lesions, which is found in the consensus molecular subtype (CMS) 1 of primary CRC tissue. Pathway analysis of these genes suggested that THCs are associated with neutrophils due to upregulation of neutrophil extracellular trap signaling (NET) and neutrophil degranulation pathways. These data provide molecular pathways for the formation of THCs suggesting fusion with neutrophils, which may facilitate extravasation and metastatic seeding.

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.