Introduction

Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer-related deaths globally, with increasing incidence and mortality rates. Most patients are diagnosed at advanced stages, missing the opportunity for radical treatment. Sorafenib, a tyrosine kinase inhibitor, is the first-line treatment for advanced HCC; however, drug resistance typically develops within 6 months. Therefore, elucidating the mechanisms of sorafenib resistance and identifying new therapeutic targets are of significant importance. Our study focuses on the role and mechanism of Ribonucleotide Reductase M2 (RRM2) in sorafenib resistance in HCC.

Aims & Methods

The primary objective of this study is to investigate the role of RRM2 in sorafenib resistance in HCC and explore its underlying mechanisms. We aim to clarify whether RRM2 regulates aerobic glycolysis via the HIF-1α/HK2 pathway, thereby affecting sorafenib sensitivity. Our methods include:

• Analyzing RRM2 expression in HCC tissues and its correlation with clinical outcomes, such as disease-free survival (DFS) and overall survival (OS).
• Establishing sorafenib-resistant HCC cell lines (LM3-SR and SMMC7721-SR) and manipulating RRM2 expression using lentiviral vectors for knockdown and overexpression.
• Conducting in vitro experiments to assess the effects of RRM2 on cell proliferation, apoptosis, glycolysis, and sorafenib sensitivity using assays such as CCK8, flow cytometry, and Seahorse analysis.
• Performing in vivo studies using a nude mouse xenograft model to evaluate the impact of RRM2 knockdown on tumor growth and sorafenib efficacy.
• Utilizing RNA-seq, Western blot, PCR, and other techniques to investigate the molecular mechanisms, including the potential regulation of HIF-1α and HK2 by RRM2.

Results

• Clinical Correlation: RRM2 expression was significantly higher in HCC tissues compared to adjacent normal tissues. Higher RRM2 levels were associated with shorter DFS and OS in HCC patients.
• In Vitro Findings: RRM2 knockdown in sorafenib-resistant HCC cells (LM3-SR and SMMC7721-SR) increased sensitivity to sorafenib, as evidenced by reduced cell viability and increased apoptosis. Additionally, RRM2 knockdown decreased glycolysis, as indicated by reduced lactate production and glucose uptake. Conversely, RRM2 overexpression in HCC cells promoted resistance to sorafenib and enhanced glycolysis.
• Molecular Mechanisms: RRM2 regulated the expression of glycolytic enzymes, particularly HK2, through the HIF-1α pathway. Knockdown of RRM2 reduced HIF-1α and HK2 expression, while overexpression of HIF-1α or HK2 could reverse the effects of RRM2 knockdown on glycolysis and sorafenib sensitivity.
• In Vivo Validation: In a nude mouse xenograft model, RRM2 knockdown enhanced the inhibitory effects of sorafenib on tumor growth, as demonstrated by reduced tumor volume and increased apoptosis.

Conclusion

Our study demonstrates that RRM2 plays a crucial role in sorafenib resistance in HCC by regulating aerobic glycolysis via the HIF-1α/HK2 pathway. Targeting RRM2 or its downstream pathways may represent a promising strategy to overcome sorafenib resistance and improve therapeutic outcomes in HCC patients. Future work will focus on further elucidating the molecular mechanisms and exploring the potential clinical applications of RRM2 as a therapeutic target.

Disclosure

The authors declare that they have no conflict of interest.

Introduction

Colorectal cancer is one of the most prevalent cancers with an estimated 1.8 million newly developed cases and 0.9 million cancer-related deaths in 2020.Resection of adenomatous polyps decreases the incidence and mortality of colorectal cancer. Narrow-band imaging (NBI) and linked color imaging (LCI) are the most predominantly conducted image-enhanced endoscopy using short-wavelength light but their usefulness in screening and surveillance colonoscopy remains controversial.

Aims & Methods

Our aim in this study was to investigate the superiority of LCI over NBI for ADR.
This is an open-label, two-arm, parallel, 1:1, multicenter, randomized, controlled, right-sided colonoscopy study and included patients who underwent colonoscopy at six endoscopy centers in Japan from November 2020 through November 2023. The patients were randomly assigned to undergo a proximal-sided colonoscopy (cecum and ascending colon) with LCI or 2G-NBI followed by WLI. The primary outcome included the ADR and secondary outcomes involved polyp detection rate (PDR), polyp miss rate, and adenoma miss rate. This study was registered on November 4, 2020, in the Japan Registry of Clinical Trials (jRCT1012200007).

Results

During the study period, 1,655 patients were randomly assigned to the LCI group (828 patients, primary LCI followed by secondary WLI) and the 2G-NBI group (827 patients, primary 2G-NBI followed by secondary WLI), and 776 patients in the LCI group and 752 patients in the 2G-NBI groups were finally analyzed. The ADRs were 26.7% and 23.4% and the PDRs were 32.6% and 28.9% in primary LCI and 2G-NBI, respectively, with no statistically significant differences in ADR and PDR between groups (P = 0.14 and P = 0.12). However, multivariate regression analysis revealed primary LCI observation as an independent predictor for reducing PDR in the secondary WLI (Odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.53−0.97, P = 0.029). Moreover, polyp analysis demonstrated that miss rates of adenomas and polyps were significantly lower in the LCI group than in the NBI group (OR: 0.54, 95% CI: 0.39−0.76 in adenoma; OR: 0.59, 95% CI: 0.44−0.78 in polyp).

Conclusion

LCI is not superior to 2G-NBI in ADR and PDR in a clinical right-sided colonoscopy setting. However, LCI significantly reduced miss rates of adenomas and polyps.

Disclosure

Naohisa Yoshida has received lecture and/or consulting fees from Fujifilm and Olympus; Shoko Ono has received lecture and/or consulting fees from Fujifilm and Olympus; Momoko Tsuda has received lecture and/or consulting fees from Fujifilm; Nobuaki Yagi have received lecture and/or consulting fees from Fujifilm and Olympus; Mototsugu Kato has received lecture and/or consulting fees from Fujifilm. The remaining authors disclose no conflicts.

Introduction

Since 2029 national curricula for sedation and emergency management in endoscopy has established for endoscopy staff. NAPS are trained in three-day courses. After a baseline assessment in 2013, the effect of the training was evaluated in a survey in 2018.

Results & Findings

The questionnaire was completed by 356 endoscopy departments (95% in hospitals, 6% in private practice).

• Most departments operate in a multidisciplinary manner (85% gastroenterology, 59% TEE, 13% cardiology, 1.12% urology).
• In 52% of departments, 100% of staff have been trained, while 30% have trained 75-100% of staff. Refresher courses are completed every 2-5 years by 77% of units, while annual resuscitation courses are established in 93% od units.
• 98% have examination rooms equipped with BB, pulse oximeter, ECG, and oxygen supply. The second suction is available in 80%, and capnography in 9%. 83% have their own recovery room, 16% use other recovery rooms.
• ASA classification is used in 80% of unit for risk assessment, while Mallampati score is used in 7% only. 38% developed department specific scores. 63% perform the sign-in for all patients, 16% for 75-100% of patients. Only 10% of departments never perform a sign-in.
• 35% of units perform team-time-out (TTO) for all patients, 11% for 75-100% of patients. Only 26% of departments never use TTO.
• In 47% of departments, a dedicated person for patient monitoring and sedation is available. 30% have this person in 75-100% of patients, and 14% have this person in 25-50% of cases.
• Propofol mono sedation by bolus application is used in 88% of units, TCI in 17% of units, combination Propofol and Midazolam is used in 27%.
• In 77% of units, inpatients and outpatient are equally monitored in the recovery area while 21% of units only use the recovery area for outpatients.
• In 73% of units, physicians discharge the patient, in 12% nurses discharge patients.
• In 80% of departments, patients are only allowed to leave the endoscopy with an accompanying person.
• 70% of departments document all complications, but only 42% evaluate the complication rate statistically.
• 42% of units reported to have no problems to establish all requirements for sedation and patient monitoring. 37% reported about staff shortage. 12% could not find new staff, 25% reported about financial problems. 44% reported about resistance in their own department or with hospital management to establish improvements.

Summary & Discussion

• Comparing data from 2013, 2018 and 2024, improvements could be identified in the establishment of riss assessment by using ASA Score and individual checklists, Malampati score is still not well-known. The establishment of TTO increased from 20 to 35% in all patients, but still needs to be improved.
• The availability of a sedating person remains unchanged with 40 to 47% in all patients and 30% in 75-100% of patients. The recovery situation remains unchanged.

Conclusion

Staff shortage and resistance within the own team are the main challenges when establishing safe sedation and patient monitoring in Endoscopy.

Disclosure

no conflict of interest

Introduction

Gastroenterologists face dual demands from clinical practice and academic research, necessitating efficient literature processing. While large language models (LLMs) show promise as healthcare tools, their variable performance in literature interpretation remains understudied, particularly regarding content completeness and reliability. This study systematically evaluates four prominent LLMs (ChatGPT-4o, Claude-3.5sonnet, Doubao-pro, Deepseek-V3) in explaining five gastroenterology literature types (original articles, case reports, reviews, editorials, guidelines), providing evidence-based recommendations for practical applications.

Aims & Methods

We tasked four LLMs with interpreting 125 gastroenterology publications (25 per literature type, 5 interpretations per article) spanning artificial intelligence, endoscopy, gastrointestinal cancers, and inflammatory bowel disease. Five gastroenterologists assessed interpretations using five criteria:
1. Accuracy: Correct identification of study design.
2. Format compliance: Adherence to predefined structure.
3. Content completeness: Key concept coverage (quantified via standardized rating scales).
4. Conciseness: Absence of extraneous content.
5. Reliability: Absence of hallucinated content.
Domain experts developed literature-specific completeness scales. Statistical analysis employed Pearson's chi-square tests for categorical variables (accuracy, format compliance, conciseness, reliability) and Kruskal-Wallis tests with Dunn's post-hoc comparisons for completeness scores. We applied Bonferroni correction for multiple comparisons (R version 4.4.2), with α=0.05 defining statistical significance.

Results

The 625 evaluations revealed significant inter-model differences across all metrics (p<0.001). ChatGPT-4o and Deepseek-V3 demonstrated superior accuracy (99.2% vs 100.0%) and format compliance (97.6% vs 99.2%) compared to Claude-3.5sonnet and Doubao-pro. Claude-3.5sonnet produced the most concise outputs (99.4%), while Deepseek showed the lowest concision (92.8%). Doubao exhibited perfect reliability (100.0%) versus 93.6%-97.0% in other models. Median completeness scores ranked: ChatGPT-4o (84.5%) > Claude-3.5sonnet (80.0%) = Doubao-pro (80.0%) > Deepseek-V3 (79.3%), with ChatGPT-4o significantly worse than others (Dunn's test, p<0.05).

Conclusion

Gastroenterologists can select LLMs based on the application priority of literature processing: ChatGPT-4o and Deepseek-V3 excel in accuracy and format compliance; Claude-3.5sonnet offers superior conciseness; while Doubao-pro demonstrates optimal reliability.

Introduction

Colon capsule endoscopy (CCE) or panenteric capsule endoscopy (PCE) offers a promising, non-invasive diagnostic approach for patients with iron deficiency anaemia (IDA). However, high rates of conversion to conventional colonoscopy (CCC) following capsule procedures reduce cost-effectiveness and patient satisfaction. Optimising the faecal immunochemical test (FIT) threshold may improve patient stratification and reduce unnecessary conversions in future applications within the IDA diagnostic pathway.

Aims & Methods

This study aimed to evaluate the accuracy of faecal immunochemical testing (FIT) in predicting colorectal cancer (CRC) and polyp burden in patients with iron deficiency anaemia (IDA), and to extrapolate these findings to assess FIT’s utility in predicting the likelihood of conversion from CCE to conventional colonoscopy (CCC) based on underlying pathology in IDA.
The CLEAR IDA study was a multicentre, retrospective observational study conducted across four UK hospitals. Data were collected over a six-month study period and included patients referred via the two-week-wait (2WW) cancer pathway for iron deficiency, with or without anaemia, over a 12-month timeframe. Colonoscopy findings were analysed and extrapolated using NHS England’s CCE-to-colonoscopy referral criteria to assess the predictive value of FIT for colorectal cancer (CRC), polyp burden, and CCC using ROC curve analysis. The optimal FIT threshold was identified through three complementary approaches: threshold-based analysis, decision curve analysis, and cost-benefit modelling.

Results

A total of 1,531 patients were analysed; only 1.6% underwent small bowel capsule endoscopy. The diagnostic accuracy (AUC) of FIT for predicting CRC, polypoidal lesions, and CCC was 0.78, 0.58, and 0.69, respectively. Threshold-based analysis identified FIT = 15 µg/g as the lowest level at which CCC rates significantly increased (p = 0.02; OR = 1.87; 95% CI: 1.07–3.14). Decision curve analysis showed maximum net benefit at FIT = 17.6 µg/g, while cost-benefit modelling identified 9 µg/g as the most cost-effective. An optimal cost-effective FIT threshold range was identified between 10 and 17.6 µg/g. Threshold selection should be tailored to local service capacity and resource availability.

Conclusion

Significant pathologies in the IDA pathway were uncommon. A FIT threshold range between 10–17 µg/g may enhance cost-effectiveness and guide appropriate PCE use in IDA.

References

1) Snook J, Bhala N, Beales ILP, et al. British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults. Gut. 2021 Nov;70(11):2030-2051.
2) (NICE) NIFHACE. PillCam COLON 2 for investigation of the colon through direct visualisation: NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE; August 2024 [cited 2025 23/03/2025]; Diagnostics Assessment Programme]. Available from: https://www.nice.org.uk/guidance/gid-dg10083/documents/final-scope-2
3) Turvill J, Haritakis M, Pygall S, et al. Multicentre Study of 10,369 Symptomatic Patients Comparing the Diagnostic Accuracy of Colon Capsule Endoscopy, Colonoscopy and CT Colonography. Aliment Pharmacol Ther. 2025 Feb 26;0:1–13.
4) Cilona A, Zullo A, Hassan C, et al. Is faecal-immunochemical test useful in patients with iron deficiency anaemia and without overt bleeding? Dig Liver Dis. 2011 Dec;43(12):1022-4.
5) Turvill JL, Turnock D, Cottingham D, et al. The Fast Track FIT study: diagnostic accuracy of faecal immunochemical test for haemoglobin in patients with suspected colorectal cancer. Br J Gen Pract. 2021 Aug;71(709):e643-e651.