Introduction

Gastrointestinal endoscopy advancements have improved diagnostics and treatment but also increased the risk of adverse events, potentially affecting the psychological well-being of practitioners. This study aims to assess the psychological state experienced by Portuguese gastroenterologists following endoscopic adverse events in endoscopic procedures.

Aims & Methods

A nationwide online survey was conducted between November 2024 and January 2025, with invitations sent to all registered Portuguese gastroenterologists (n=709). Psychological state was assessed using validated scales assessing psychological distress (DASS-21), professional quality of life (ProQOL-5), self-compassion (SCS-12), and shame feelings (OAS2). Results are presented as median (Mdn) and interquartile range (IQR).

Results

Seventy gastroenterologists participated in the study (Mdn age 41 years; experience 11 years; both IQR 11), with a 9.87% participation rate. Nearly all (n=69) had encountered adverse events, with most reporting 1–5 incidents. None sought psychological support after the adverse events, 6 faced legal repercussions, and 3 discontinued specific techniques. DASS-21 had a Mdn of 6.00 (IQR 12.00) for stress (mild if <10), 4.00 (IQR 8.00) for anxiety (mild if <6), and 4.00 (IQR 6.00) for depression (mild if <10). ProQOL-5’s total score Mdn was 41.00 (IQR 6.50) for compassion satisfaction, 25.5 (IQR 7.00) for burnout, and 24.00 (IQR 6.25) for traumatic stress, all within the moderate range (23–41). OAS2 shame score was 16.00 (IQR 7.30). Self-compassion showed a Mdn of 3.46 (IQR 1.00; moderate if 2.3–3.5). Gastroenterologists with legal repercussions had higher compassion satisfaction (52.50 vs. 33.33; p = 0.025). Those who discontinued procedures reported higher anxiety levels (56.17 vs. 31.88; p = 0.026), but no other significant differences were found.

Conclusion

This is the first published study assessing the psychological state of adverse events on gastroenterologists. While most reported mild to moderate distress, legal repercussions were associated with higher compassion satisfaction, and stopping procedures correlated with higher anxiety. Findings suggest a need for psychological support after endoscopic adverse events, and for research on their impact on gastroenterologists.

Introduction

Spontaneous bacterial peritonitis (SBP) is a well-recognized decompensation that significantly affects the clinical outcome of patients with liver cirrhosis. The aim of this study is to assess the factors associated with short-term mortality in this patient population.

Aims & Methods

We conducted a retrospective study (January 2022 to December 2024) on all cirrhotic patients with SBP, admitted in the Gastroenterology Department of “St. Spiridon” County Clinical Emergency Hospital Iasi, a tertiary referral center. The SBP cases were identified based on elevated ascitic fluid absolute PMN count > 250 cells/mm³, with or without positive ascitic fluid bacterial culture.

Results

Out of the 114 cirrhotic patients diagnosed with SBP for the first time, 39 (34,2%) were female and 75 (65,8%) were male, with a mean age of 57 years. Most patients had advanced liver disease according to the Child-Pugh classification: 98 patients (86%) were classified as Child C, and 16 patients (14%) as Child B. The mean MELD-Na score was 23.3 points. The overall in-hospital mortality rate was 17.5% (20 patients). According to the multivariable analysis, several factors were significantly associated with in-hospital mortality, such as: renal dysfunction (OR 8.4118 [95% CI 2.9190 to 24.2403]; P=0.0001), serum bilirubin higher than 3 mg/dl (OR 4.8571 [95% CI 1.7445 to 13.5216]; P=0.0025), serum sodium lower than 130 mmol/l (OR 4.3750 [95% CI 1.5973 to 11.9833]; P=0.0041), international normalized ration (INR) higher than 2 (OR 4.5222 [95% CI 1.6471 to 12.4161]; P=0.0034).

Conclusion

Renal dysfunction, elevated INR, hyperbilirubinemia, and hyponatremia appear to be significant factors associated with the worsening of prognosis in cirrhotic patients with SBP, influencing in-hospital mortality.

Introduction

Recent studies have revealed that liquid-liquid phase separation (LLPS) plays a critical role in tumorigenesis. Myotilin (MYOT), a key component of actin cross-linking protein complexes, is involved in regulating myofibril assembly and maintaining the structural integrity of Z-discs in muscle cells. Intriguingly, MYOT contains intrinsically disordered regions (IDRs) and has been implicated in the migration of gastric cancer. However, whether MYOT undergoes LLPS and whether this process contributes to gastric cancer progression remains unexplored.

Aims & Methods

We aimed to investigate whether MYOT undergoes LLPS and its potential role in gastric cancer progression.
Differential gene expression analysis was performed on gastric cancer samples from our sequencing data and validated using public databases. The Disprot, Database of Protein Disorder was used to predict the IDRs of MYOT. Fluorescence recovery after photobleaching (FRAP) and cellular immunofluorescence were explored to assess MYOT’s ability to undergo LLPS. Cell proliferation, apoptosis and migration assay were conducted to investigate the potential role of MYOT in gastric cancer. Actin polymerization assays were performed to evaluate the qualitative effects of purified MYOT on actin polymerization.

Results

Differential gene expression analysis revealed that MYOT was significantly downregulated in gastric cancer tissues compared to adjacent normal tissues, a finding further confirmed by RT-qPCR. In the prediction of protein structure, it can be found that MYOT contains extensive IDRs. FRAP analysis demonstrated rapid fluorescence recovery in GFP-MYOT droplets within minutes, suggesting dynamic LLPS behavior. Similarly, purified GFP-MYOT exhibited fusion behaviors, further supporting its capacity for LLPS in vitro. Overexpression of MYOT did not significantly affect gastric cancer cell proliferation or apoptosis, but reduced cell migration. Actin polymerization failed to occur both in the GFP-MYOT and GFP control samples.

Conclusion

Our findings demonstrate that MYOT suppresses gastric cancer cell migration and purified GFP-MYOT does not directly promote on actin polymerization, implicating its potential role as a tumor suppressor. Additionally, MYOT undergoes LLPS both in vitro and in vivo, as evidenced by FRAP. We propose that MYOT may exert its anti-tumor effects through LLPS-mediated mechanisms, offering a novel perspective on its function in gastric cancer progression.

Introduction

Endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (SESCC) involving the entire circumference carries the extremely high risk of stricture and also raises concerns about curative resection. Therefore, the current Japanese guidelines weakly recommend ESD only for circumferential SESCCs diagnosed as cEP/LPM and sized ≤ 50 mm, while surgery or chemoradiotherapy (CRT) is recommended for circumferential SESCCs other than the above. ¹ However, in clinical practice, ESD is implemented on a case-by-case basis through the discussion in a multi-disciplinary cancer board at each institution because the outcomes of each treatment for circumferential SESCCs remain unclear.²

Aims & Methods

This multicenter prospective observational study aimed to reveal the outcomes of each treatment for circumferential SESCCs. Patients with cT1a-EP/LPM or cT1a-MM/T1b-SM1 N0M0 SESCCs involving the entire circumference were enrolled in this study. At this stage, short-term outcomes, such as the proportion of curative resection after ESD, complete response (CR) after CRT/radiotherapy (RT), and adverse events including esophageal stricture, were evaluated. Curative resection in ESD was defined as pT1a without lymphovascular invasion (LVI). Esophageal stricture was defined as inability to pass the ordinary-sized endoscope thorough the treated site, and refractory stricture was defined as stricture requiring ≥ 6 endoscopic balloon dilation procedures.

Results

A total of 126 patients with circumferential SESCCs were enrolled from 16 Japanese tertiary institutions between May 2021 and November 2024. ESD was performed for 90 (71.4%) patients including 6 undergoing stepwise ESD, surgery for 18 (14.3%), CRT for 16 (12.7%), and RT alone for 2 (1.6%). Median longitudinal length of tumor was 55 (range: 30–140) mm in the ESD group, 80 (50–150) mm in the surgery group, and 70 (30–100) mm in the CRT/RT group. Tumor depth was diagnosed as cEP/LPM in 65.4% (55/84) of the ESD group, 38.9% (7/18) of the surgery group, and 50.0% (9/18) of the CRT/RT group, and the others were diagnosed as cMM/SM1. As stricture prevention method after ESD, local injection or filling of triamcinolone (TA) alone was used in 9 patients (10.7%), and both local injection of TA and oral steroid of prednisolone were used in 75 (89.3%). Among the 63 patients who did not receive additional treatment after ESD, the proportion of stricture and refractory stricture were 46.0% (29/63) and 27.0% (17/63), respectively. Curative resection after ESD was achieved in 58 patients (69.0%), including 46 (83.6%) with cEP/LPM and 12 (41.4%) with cMM/SM1. Of 26 patients with non-curative resection after ESD, 20 (76.9%) received additional treatment of either surgery, CRT, or RT, while the remaining 6 opted for follow-up. Of 18 patients in the surgery group, 7 with cEP/LPM and 4 with cMM/SM1 were diagnosed as pT1aN0 without LVI, while the remaining 7 with cMM/SM1 were diagnosed as pT1b, 3 of whom had lymph node metastasis. Anastomotic stricture was observed in 11.1% (2/18) of patients treated with surgery. Of 18 patients in the CRT/RT group, CR was confirmed in all patients without forming stricture.

Conclusion

Considering the high curative resection rate, ESD could be indicated for circumferential SESCCs diagnosed as cEP/LPM. In contrast, the careful consideration may be required in indicating ESD for circumferential SESCCs diagnosed as cMM/SM1 due to its low curative resection rate. Long-term outcome needs to be confirmed for further treatment comparisons.

References

1. Ishihara R, Arima M, Iizuka T, et al. Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer. Dig Endosc. 2020; 32: 452–93.
2. Kadota T, Ishihara R, Hatta W, et al. Multi-institutional questionnaire on treatment strategies for superficial entire circumferential esophageal squamous cell carcinoma. DEN Open. 2023; 3: e206.

Introduction

Current colonoscopy quality indicators recommend a minimum withdrawal time (WT) of 6 minutes. However, this standard may reduce colonoscopy efficiency and does not account for endoscopists' experience or bowel preparation quality. This study aims to investigate whether the 6-minute WT remains necessary for experienced endoscopists with excellent bowel preparation (BBPS≥8) by comparing the impact of 5-minute versus 6-minute WT on adenoma detection rate (ADR) and adenoma miss rate (AMR).

Aims & Methods

This study based experienced endoscopists and excellent bowel preparation (Boston Bowel Preparation Scale score, BBPS≥8) is aimed to compare the effect of 5-minute WT versus 6-minute WT on adenoma detection rate (ADR) and adenoma miss rate (AMR).
This multicenter, randomized controlled trial involving 423 patients was conducted from June 2023 to March 2025 in 5 centers, including Wuxi People's Hospital, Jiangsu Province People's hospital, Xuzhou First People's Hospital, The Second Affiliated Hospital of Soochow University, Taizhou People's Hospital. Colonoscope was inserted and withdrew twice on each patient and all procedures for the same patient were done by the same endoscopist. Participants were randomly divided into the 5-minute WT group (the first WT-5-minute and the second WT-6-minute, n =214) and the 6-minute WT group (the first WT-6-minute and the second WT-6-minute, n=209), and a timer was used to adjust the withdrawal speed. The primary outcome was ADR and AMR.

Results

The baseline characteristics of the two groups were similar (Table 1) and colonoscopy characteristics of the patients in the two groups regarding quality of bowel preparation, cecal intubation rate, cecal intubation time, cecal intubation distance, number of abdominal compression, number of position change were comparable (Table 2). Overall ADR (39.7% vs 43.5%, P = 0.425), ADR in the first (36.0% vs 36.4%, P = 0.935) and second withdrawal (10.7% vs 13.9%; P = 0.327) were not significantly increased in the 6-minute WT group compared with the 5-minute WT group. Likewise, the overall advanced adenoma detection (AADR) (4.7% vs 5.3%, P = 0.780), AADR in the first (4.7% vs 5.3%, P = 0.780) and second withdrawal (0.5% vs 0.5%, P = 0.745) did not differ statistically. Further analysis showed that AMR (10.7% vs 13.9%, P = 0.372) was lower in the 5-minute WT group than in the 6-minute WT group, less adenomas were missed in the 5-minute WT group, although not statistically significant (Table 3).
Table 3. Lesion-level detection and miss rate in the two groups
PDR, polyp detection rate; ADR, adenoma detection rate; AADR, advanced adenoma detection rate; AMR, adenoma miss rate; AAMR, advanced adenoma miss rate; PMR, polyp miss rate.
Table 3. Lesion-level detection and miss rate in the two groups

Conclusion

Shortening WT from 6 to 5 minutes didn't reduce ADR based experienced endoscopists and excellent BBPS, a 5-minute WT benchmark was acceptable with experienced endoscopists and excellent bowel preparation quality of colonoscopy.

Introduction

Accurate prediction of lymph node metastasis (LNM) in submucosal invasive (T1) colorectal cancer (CRC) is essential for determining the need for additional surgery following endoscopic resection. Conventional histopathological assessments, however, are limited by interobserver variability. This study aimed to develop and externally validate a stacking-based artificial intelligence (AI) model integrating histopathological whole slide images (WSIs) and clinical parameters to predict the risk of LNM in T1 CRC.

Aims & Methods

This retrospective study included 1,056 patients with histologically confirmed T1 CRC treated at Showa Medical University Northern Yokohama Hospital. Of these, 593 cases were used for model training and 100 for internal testing. External validation was conducted on 25 cases from two independent institutions.
The proposed stacking ensemble model incorporated the Multiple Instance Self-Training (MIST) score derived from WSIs, patient sex, and tumor location (colon vs. rectum). Base learners included logistic regression, XGBoost, and random forest, with a meta-learner synthesizing their outputs to generate the final LNM prediction. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) in both internal and external cohorts.

Results

LNM was observed in 69 (11.6%) training cases, 15 (15.0%) test cases, and 2 (8.0%) external validation cases. The model achieved an AUC of 0.6965 in the internal test cohort and 0.7500 in the external validation cohort, demonstrating stable and generalizable predictive performance.
A representative case involved a 64-year-old man with a 16-mm type 0-Is lesion in the sigmoid colon resected via endoscopic mucosal resection (EMR). Histopathology showed well-differentiated tubular adenocarcinoma (tub1 > tub2), submucosal invasion depth of 3,300 µm (T1b), tumor budding grade BD1, Ly0, V1a, and negative resection margins (HM0, VM0). Despite guideline-based recommendations prompting additional surgical resection, no LNM was found (N0, 0/16), and the patient remained recurrence-free five years postoperatively—consistent with the AI model’s prediction.

Conclusion

The stacking-based AI model exhibited robust and generalizable performance in predicting LNM in T1 CRC, both internally and across external institutions. This approach offers a complementary tool to conventional pathology and may enhance individualized decision-making regarding the necessity of additional surgical intervention.

Introduction

The lymphocyte-to-monocyte ratio (LMR) is widely utilized as a surrogate marker of systemic inflammation and is increasingly recognized as an indicator of immune status within the tumor microenvironment, particularly in the setting of cancer immunotherapy.

Aims & Methods

^​​​​​This study aimed to evaluate the prognostic relevance of LMR in patients undergoing combination therapy with durvalumab (Dur) and tremelimumab (Tre) for unresectable hepatocellular carcinoma (uHCC). A total of 242 patients with uHCC who received Dur/Tre therapy at multiple institutions between February 2023 and March 2025 were retrospectively analyzed. Inclusion criteria encompassed available baseline LMR, Child-Pugh class A liver function, and complete clinical data. Patient characteristics were as follows: median age 74.0 years (IQR: 68.3–77.0); sex distribution, 202 males and 40 females; performance status (PS) 0/1/≥2: 201/32/9; underlying liver disease (HBV/HCV/HBV+HCV/NBNC): 37/72/1/132; BCLC stage (≤A/B/≥C): 19/68/155; Child-Pugh score (5/6): 125/117; alpha-fetoprotein (AFP) level: 57.6 ng/mL (IQR: 4.3–909.8); LMR: 3.14 (2.18–4.15); treatment line (first-/second-line): 94/148; and median observation period: 9.0 months (5.0–14.2).

Results

The median progression-free survival (PFS) and overall survival (OS) were 3.5 months (2.8–4.3) and 19.2 months (15.4–NA), respectively. Time-dependent ROC analysis identified 2.15 as the optimal LMR cutoff at 25% of the observation period (15.4 months). Objective response rates per RECIST version 1.1 were as follows: complete response (CR), 3.2%; partial response (PR), 15.5%; stable disease (SD), 32.4%; and progressive disease (PD), 48.9%. Disease control rate (DCR) was significantly higher in the LMR ≥2.15 group compared to the <2.15 group (55.4% vs. 37.3%, p = 0.026). Patients with LMR ≥2.15 demonstrated significantly longer PFS (3.8 months [95% CI: 3.8–4.6] vs. 2.7 months [95% CI: 2.00–4.00]; p= 0.005) and OS (NA months [95% CI NA: –17.9] vs. 13.2 months [95% CI: 8.5–17.1]; p = 0.005). In multivariate analysis using the Cox proportional hazards model, LMR ≥2.15 emerged as an independent predictor of both PFS (HR = 0.622; 95% CI: 0.438–0.884; p = 0.008) and OS (HR = 0.558; 95% CI: 0.328–0.949; p = 0.031). Hazard ratio approximation curves indicated that the range of LMR associated with significant prognostic impact on both PFS and OS was approximately 1.6 to 2.4. Subgroup analysis further demonstrated that in first-line treatment settings, patients with LMR ≥2.15 had superior PFS and OS outcomes compared to those with LMR <2.15 (PFS: p = 0.028; OS: p = 0.016).

Conclusion

​​​​LMR serves as a valuable prognostic biomarker in patients receiving Dur/Tre combination therapy for uHCC, with potential utility in guiding therapeutic decision-making.

Disclosure

Toshifumi Tada: lecture fees from AbbVie, Eisai, and Chugai
Atsushi Hiraoka: lecture fees from Eisai, Bayer, Eli Lilly, and Otsuka
Hidenori Toyoda: lecture fees from AbbVie, Eisai, Gilead, Terumo, and Bayer