Introduction

Endoscopic submucosal dissection (ESD) stands as the gold standard treatment of gastric superficial lesions. Due to its technical complexity, ESD procedures often require extended durations, and longer procedural times are related to a higher level of adverse events. We intend to analyze our procedural time according to the predictive formula developed by Goto et al.

Aims & Methods

Prospective cohort study, single center, of patients who underwent gastric ESD between 2017 and 2023. The characteristics of the lesion were evaluated, and logistic regression of risk factors associated with longer procedural time (≥ 60 minutes) was performed. The predictive formula of procedural time was calculated for each patient and comparison between predictive and actual procedural time was performed using Pearson correlation coefficient.

Results

Included 101 gastric ESDs, 63.4% female, with a mean age of 69.7 ± 8 years. Among the analyzed lesions: 43.6% measured between 0-20mm, 56.4% ≥ 20mm; 13.9% were sessile, 60.4% flat, 14.9% depressed and 10.9% subepithelial; 22.8% were located in the upper-third of the stomach, 17.8% in the middle-third and 59.4% in the lower-third. Ulcerative findings were identified in 10% of the lesions. The most frequent histological results were: 38.6% low grade dysplasia, 26.7% high grade dysplasia and 19.8% intramucosal adenocarcinoma. The mean procedure duration was 87±43 minutes. Intra-procedure adverse events registered in 2% (perforation).
Evaluating the risk factors for longer procedures (≥ 60 minutes), the following revealed statistical significance: lesion size ≥ 20mm (89.5% vs. 65.9%; p=0.004), histology indicative of intramucosal adenocarcinoma (95.7% vs. 74.4%; p=0.027) and location in the upper or middle-third of the stomach (95.1% vs. 68.3%; p=0.001), but not the Paris classification (78.6% vs. 75.4% vs. 93.3%; p=0.4), ulcerative findings (63.6% vs. 67.1%; p=0.8) and the use of anticoagulant therapy (64.3% vs. 81.6%; p=0.138). Logistic regression analysis revealed that lesion size ≥ 20mm (OR 5.7; IC95%: 1.7-18.7) and location in the upper or middle-third of the stomach (OR 13.6; IC95%: 2.3-80.7) were significantly associated with longer procedural time.
When comparing predicted and actual procedural time, the overall Pearson correlation coefficient (r) was 0.58 (p<0.01), with the following values per consecutive 25 cases: 0.70, 0.67, 0.54 and 0.46.

Conclusion

Previous identification of risk factors for prolonged ESD procedures, such as lesion size ≥ 20mm and proximal lesion location, can be useful in optimizing workflow scheduling. Our correlation between predicted and actual time demonstrated a decreasing value, probably due to a higher complexity of the lesions, giving room for improvement.

Introduction

Chimeric antigen receptor (CAR) T cells have shown remarkable efficacy in hematological malignancies, but remain largely ineffective in solid tumors such as pancreatic ductal adenocarcinoma (PDAC). Major barriers include CAR-T cell dysfunction, poor infiltration, and limited persistence within the immunosuppressive tumor microenvironment. STING (stimulator of interferon genes) activation can remodel this environment by inducing inflammation and reversing cancer immune privilege. However, the use of STING agonists in combination with CAR-T cells is hampered by T cell-intrinsic STING signaling, which induces T cell dysfunction and apoptosis.

Aims & Methods

To overcome these limitations, we investigated the therapeutic potential of combining STING agonists with CAR-T cells genetically ablated for STING for the treatment of PDAC. Using CRISPR-Cas9-edited CAR-T cells and the STING agonist diABZI, we assessed antitumor activity in vitro using a CAR-T cell exhaustion model and in vivo using both a cell line-derived xenograft and a syngeneic mouse model.

Results

The combination of STING^KO CAR-T cells and diABZI substantially enhanced CAR-T cell function. In vitro, we observed improved tumor cell killing, increased CAR-T cell proliferation, reduced expression of exhaustion markers, and expansion of an effector-memory phenotype. These effects required genetic deletion of STING in CAR-T cells and were dependent on cancer cell-intrinsic STING signaling. Mechanistically, we identified a synergistic feedback loop, in which CAR-T cell-derived IFN-γ and TNF-α enhanced STING signaling in cancer cells, further promoting beneficial CAR-T cell states. In vivo, this combination achieved superior tumor control in both xenograft and syngeneic mouse models.

Conclusion

Our findings demonstrate that STING^KO CAR-T cells can be effectively combined with STING agonists to enhance therapeutic efficacy in immune-cold tumors such as PDAC. This strategy represents a promising approach to overcoming current barriers in CAR-T cell therapy for solid tumors.

Disclosure

I.P. reports reimbursement of travel expenses from Roche and received third-party funding for scientific research from Novartis. A.G. received research support from Tabby Therapeutics and from Nanogami for work unrelated to the paper. M.S. has received research funding from Amgen, BMS/Celgene, Gilead/Kite, Janssen, Miltenyi Biotech, Molecular Partners, Novartis, Roche, Seagen and Takeda, honoraria from AbbVie, Amgen, AvenCell, BMS, CanCell Therapeutics, Gilead, Janssen, Miltenyi Biomedicine, Molecular Partners, Pfizer and Roche and was invited as speaker by AstraZeneca, BMS, Gilead/Kite, GSK, Janssen, LAWG, Novartis, Pfizer, Roche and Springer Healthcare. S. K. has received honoraria from Cymab, Plectonic, TCR2 Inc., Miltenyi, Galapagos, Novartis, BMS and GSK. S. K. is an inventor of several patents in the field of immuno-oncology. S. K. received license fees from TCR2 Inc and Carina Biotech. S.K. received research support from TCR2 Inc., Tabby Therapeutics, Catalym GmBH, Plectonic GmBH and Arcus Bioscience for work unrelated to the manuscript. The other authors have no competing interests to declare.

Introduction

Endoscopic submucosal dissection (ESD) is a valuable technique for the en-bloc resection of superficial neoplasms in the anal canal. However, its safety and efficacy in patients who have previously undergone transanal endoscopic surgery (TES) —such as transanal minimally invasive surgery (TAMIS) and transanal endoscopic microsurgery (TEM)—remain unclear.

Aims & Methods

To assess the safety and outcomes of ESD in the anal canal for patients with a history of TES compared to naïve patients.
A retrospective analysis was conducted at our tertiary center on 51 patients who underwent ESD in the anal canal between March 2010 and November 2024. Patients with a history of transanal endoscopic surgery were compared to those undergoing ESD as their primary treatment. Key parameters, including resection speed, perforation rates, coagrasper usage, inpatient status, late hemorrhage, and recurrence, were evaluated. Statistical analysis was performed to determine significant differences between groups.

Results

Histological examination confirmed the following cases: 3 adenocarcinomas (including 1 non-curative ESD), 15 adenomas with high-grade dysplasia, 11 adenomas with low-grade dysplasia, 2 sessile serrated lesions, 15 sessile serrated lesions with dysplasia, 2 high-grade intraepithelial lesions, 2 low-grade intraepithelial lesions.
The median resection velocity was slightly lower in patients with recurrence (16.01 mm²/min) compared to those without recurrence (25.56 mm²/min), though this difference did not reach statistical significance (p = 0.062). Perforation occurred in 9.62% of cases, with similar rates between groups (p = 0.58), suggesting that prior TEM does not significantly increase the risk of this complication. Late hemorrhage was observed in 7.84% of patients, again without a significant difference between groups (p = 0.29).
The only statistically significant finding was the smaller lesion size in patients with recurrence (1,162 mm² vs. 2,250 mm², p = 0.045). This is likely due to intensive post-TEM surveillance, which allowed for early detection of recurrence before lesions could grow larger. Other factors, including sex, age, use of coagrasper during the procedure, en-bloc resection, R0 status, and inpatient admission rates, showed no significant differences between groups.

Conclusion

ESD in the anal canal after prior TES appears to be a safe and feasible procedure, with outcomes statistically comparable to those in naïve patients. Although absolute numbers suggest differences, particularly in lesion size, these findings may be influenced by the small sample size. Larger studies are needed to confirm these results and further evaluate long-term efficacy.

Introduction

Gastrointestinal endoscopy is considered a key examination in the setting of anemia workup. However, the yield of esophagogastroduodenoscopy (EGD) and colonoscopy varies depending on the patient's presentation and the type of anemia.

Aims & Methods

The aim of our study was to evaluate the efficiency of EGD and colonoscopy in adult patients with anemia. We retrospectively analysed patients who underwent EGD or colonoscopy for anemia workup in our department between 2018 and 2024. Patients with symptoms suggestive of another cause of anemia were excluded. Additionally, patients who presented with gastrointestinal symptoms and patients with a history of gastrointestinal disease or surgery that could be related to the occurrence of the anemia were also excluded.

Results

A total of 564 patients were included in the study, with a mean age of 72 ±12.8 years. The majority of patients were women (52.8%). 84.9% of the patients underwent EGD, and 49.8% underwent colonoscopy. Overall, 34.8% of patients underwent both examinations. Furthermore, an additional 17.5% were not required to undergo the second examination due to a concrete cause of anemia being found in the initial examination, raising the percentage of patients who completed evaluation to 295 (52.3%). Most of the patients had iron deficiency anemia (IDA) (68.7%). 163 (28.9%) patients had an endoscopic finding that was considered the cause of anemia. EGD yielded significant findings in 119 (24.8%) patients, and colonoscopy in 46 (16.4%) patients. The most prevalent finding of colonoscopy was colon cancer (27 patients), while the most prevalent findings of EGD were peptic ulcer disease (37 patients), stomach cancer (24 patients), and severe atrophic gastritis (18 patients). There was a significant association between the type of anemia and the diagnostic yield of endoscopy, with endoscopic findings being significantly more prevalent in patients with IDA (36.1%) compared to patients without (13.8%) (p < 0.001).

Conclusion

Gastrointestinal endoscopy is the cornerstone examination in patients with unexplained IDA. Conversely, in patients with non-IDA anemia, while endoscopy retains significant diagnostic value, a simultaneous workup for other causes outside the gastrointestinal system is also indicated.

Introduction

Intestinal point-of-care ultrasound, as standardized by the International Bowel Ultrasound Group (IBUS), has emerged as a valuable tool for diagnosing, monitoring, and managing patients with Inflammatory Bowel Disease (IBD). While IBUS emphasizes a structured intestinal assessment, some European centers adopt a more comprehensive approach, combining intestinal ultrasound with a complete abdominal examination.
The Karolinska Centre for Digestive Health, a tertiary referral institution providing specialized care to approximately 4,500 patients with IBD, established a dedicated Gastrointestinal Ultrasound Unit in October 2023. This unit offers advanced diagnostic services to both hospitalized patients and those treated on an outpatient basis.

Aims & Methods

This retrospective study aimed to assess the prevalence of secondary extraintestinal findings in IBD patients undergoing comprehensive abdominal ultrasound between October 4, 2023, and March 4, 2025. All patients underwent ultrasound assessments that included both intestinal and abdominal imaging. Patients referred for indications unrelated to intestinal ultrasound (IUS), as well as those undergoing repeat examinations, were excluded from the analysis to ensure data consistency.
All examinations were performed by a single gastroenterologist with 25 years of ultrasound experience. In cases where secondary extraintestinal findings were identified, patients’ electronic medical records were reviewed to determine whether these findings represented new diagnoses or previously known conditions.

Results

The study included 348 patients with IBD, 201 (58%) females and 147 (42%) males, with a mean age of 42.4 years. Among these, 260 (75%) were referred internally by our IBD Outpatient Clinic, 47 (13%) by the Gastroenterology Ward, 33 (10%) by private outpatient clinics, and the remainder from other healthcare sites. IUS revealed evidence of intestinal inflammation in 144 patients (42%), while findings were normal in 204 patients (58%).
Furthermore, 150 patients presented with a total of 195 secondary extraintestinal findings, of which 113 (58%) represented newly identified pathologies. Among all secondary findings, the majority, 104 (53%), were related to the hepatobiliary system, including 33 newly diagnosed cases of hepatic steatosis and 17 new cases of cholecystolithiasis. One patient demonstrated ultrasound features suggestive of primary sclerosing cholangitis (PSC) and is currently undergoing further evaluation. Additional findings involved the reproductive system (29/15%), urinary system (15/7%), spleen (32/16%), and pancreas (5/2%). Various other intra-abdominal findings were also identified (37/18%). Notably, one patient presented with a suspicious mass in the right iliac fossa, and another demonstrated ultrasound findings suggestive of a prostatic tumor; both cases were referred for further oncologic evaluation. Additionally, three patients were newly diagnosed with intraductal papillary mucinous neoplasm (IPMN), which was subsequently confirmed via magnetic resonance imaging, and all were enrolled in the national IPMN surveillance protocol.

Conclusion

A considerable proportion of patients with IBD were found to have previously unknown extraintestinal abdominal pathologies, underscoring the essential role of comprehensive ultrasound examination that combines both intestinal and abdominal assessment. Fortunately, only a minority of these findings resulted in changes to patient management.

Disclosure

Francesca Bresso has acted as national and/or local principal investigator for clinical trials for Janssen, Ferring, and AbbVie. Charlotte Hedin served as a speaker and/or advisory board member for AstraZeneca, AbbVie, Dr. Falk Pharma and the Falk Foundation, Galapagos, Janssen, Pfizer, Ferring, Takeda, and Tillotts Pharma and received grant support from Tillotts Pharma and Takeda. Stephan L. Haas has served as a speaker for Takeda, Santax Medico, Tillotts Pharma, Johnson & Johnson, and Mediahuset. The rest of the authors have nothing to declare.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease frequently associated with type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aims to quantify the prevalence of NAFLD and non-alcoholic steatohepatitis (NASH) among individuals with T2DM and evaluate the spectrum of liver fibrosis within this cohort.

Aims & Methods

Medline and Embase databases were searched to identify relevant studies published in English, from inception until 13th February 2023. Original articles reporting crude data necessary to calculate the prevalence of NAFLD or NASH in a T2DM population were included. NAFLD was diagnosed based on the criteria set by the American Association for The Study of Liver Diseases (AASLD) guidelines, while liver biopsies were required to identify NASH. Fibrosis was evaluated through non-invasive and invasive techniques.
T2DM was defined by glycohemoglobin ≥ 6.5%, fasting plasma glucose ≥ 7mmol/l, self-reported diabetes, or use of anti-diabetic medications.

Results

124 studies consisting of 1,689,498 individuals with T2DM were analysed. The prevalence of NAFLD in T2DM patients from population-based settings was 57.93% (95% CI: 49.55% to 65.88%). The pooled prevalence of NAFLD was 63.71% (95%CI: 59.94% to 67.32%), while the pooled prevalence of NASH was 31.46% (95%CI: 14.25% to 55.91%). Interestingly, the prevalence of NASH in T2DM patients was 49.55% (95% CI: 28.31% to 70.95%) in Western countries, while only 9.73% (95% CI: 1.84% to 38.28%) in Eastern countries. The frequency of clinically significant fibrosis (F2-4) was 19.82% (95%CI: 13.13% to 28.80%), and the frequency of advanced fibrosis (F3-4) was 14.08% (95%CI: 10.21% to 19.10%) among T2DM patients with NAFLD. This increased to 37.48% (95%CI: 22.16% to 55.80%) and 36.54% (95%CI: 19.05% to 58.49%) respectively among T2DM patients with NASH.

Conclusion

There is a high prevalence of NAFLD and NASH in individuals with T2DM, with nearly a fifth of T2DM individuals with NAFLD affected by liver fibrosis. Clinical management of patients with T2DM should include specific interventions aimed at the targeted prevention, diagnosis and management of NAFLD and its complications.