Introduction

Endoscopic mucosal resection (EMR) of colonic lesions is widely used for the removal of superficial gastrointestinal neoplasms, but intraprocedural and postprocedural bleeding remain significant adverse events. Current strategies often involve epinephrine injection, which has uncertain efficacy and potential systemic side effects, including hypertension and increased postprocedural pain. Tranexamic acid (TXA), an antifibrinolytic agent with a well-established safety profile, has shown efficacy in reducing bleeding across various surgical fields and may be an alternative to epinephrine use.

Aims & Methods

The primary aim was to assess whether the addition of TXA into the submucosal injection solution during colonic EMR is non-inferior to epinephrine in reducing the rates of intraprocedural and postprocedural bleeding. Secondary aims included comparing pain levels, the need for opioid analgesia, and the incidence of other complications such as deep mural injury and delayed bleeding. A prospective, double-blinded, controlled, non-inferiority pilot study was conducted at the Shamir Medical Center. Patients aged >18 years undergoing EMR for colonic lesions ≥20 mm were randomized into two groups. The study group received a standard injectate solution with 100 mg TXA in 10 ml, while the control group received the same solution with 1:100,000 epinephrine. Outcome measures included intraprocedural bleeding, delayed bleeding, pain (and analgesic use), perforation, hospitalization, and post-polypectomy syndrome.

Results

A total of 112 patients were included (57 TXA, 55 epinephrine). The mean age of the entire cohort was 69.0 years, and 47.3% were women. The average polyp size was 33.4 mm. The groups were comparable in most baseline characteristics, although TXA patients were slightly older (p = 0.032) and had higher rates of diabetes (p = 0.042). No significant difference was observed in lesion size, morphology, or pathology. Intraprocedural bleeding was similar across groups. Clinically significant delayed bleeding occurred in 7% of TXA vs 7.3% of epinephrine patients (p = 0.958). Notably, postprocedural pain was significantly reduced in the TXA group (5.3% vs 41.8%, p < 0.001), as was opioid requirement (0% vs 47.8%, p < 0.001). Although not statistically significant, there were no cases of deep mural injury or hospitalization due to post-polypectomy syndrome in the TXA group, compared to four in the epinephrine group (p = 0.055).

Conclusion

The addition of TXA to the submucosal injection solution during colonic ER procedures is non-inferior to epinephrine in preventing intraprocedural and delayed bleeding. Moreover, TXA is associated with significantly reduced postprocedural pain and opioid use, suggesting it may offer a safer and more comfortable alternative to epinephrine. These findings support the feasibility of larger-scale trials to further evaluate the efficacy and safety of TXA in endoscopic interventions.

Introduction

Gastroesophageal reflux disease (GERD) and asthma are commonly co-occurring conditions, with shared genetic factors identified. However, the specific loci and the influence of common genetic architecture remain undefined.

Aims & Methods

We obtained genome-wide association study (GWAS) summary statistics for GERD (71,522 cases, 261,079 controls) and asthma (56,167 cases, 352,255 controls). Using linkage disequilibrium score regression (LDSC), we assessed genetic correlations between GERD and asthma. Bidirectional mendelian randomization (MR) was performed to investigate potential causal relationships, followed by cross-trait GWAS meta-analysis and colocalization analysis to identify shared risk loci. Additionally, summary-data-based mendelian randomization (SMR) and transcriptome-wide association study (TWAS) were conducted to pinpoint common functional genes. Finally, we analyzed gene expression profiles in both healthy individuals and GERD patients using esophageal single-cell RNA sequencing (scRNA-seq) data.

Results

We identified a significant genetic correlation between GERD and asthma (r_g = 0.37, P = 6.19×10^–38) and a significant causal effect of GERD on asthma (OR = 1.22, P = 1.54×10^-5). Cross-trait meta-analyses revealed 56 shared risk loci between GERD and asthma, including 51 loci that were newly identified. Three loci (rs61937247, rs7960225, and rs769670) exhibited evidence of colocalization. Gene-level analyses pinpointed three novel shared genes(RBM6, SUOX, and MPHOSPH9) between GERD and asthma. Single-cell RNA sequencing analysis uncovered heightened expression of these genes in immune cells of patients diagnosed with GERD.

Conclusion

Our study has discovered novel shared genetic loci and candidate genes between GERD and asthma, providing further insights into the genetic susceptibility of comorbidity and potential mechanisms of the two diseas​​​​es.

References

1. Broers C, Tack J, Pauwels A. Review article: gastro-oesophageal reflux disease in asthma and chronic obstructive pulmonary disease. Aliment Pharmacol Ther 2018;47:176–191.
2. Eapen AA, Gupta MR, Lockey RF, et al. Gastroesophageal reflux disease, laryngopharyngeal reflux, and vocal cord dysfunction/inducible laryngeal obstruction-overlapping conditions that affect asthma. J Allergy Clin Immunol. 2024;154(6):1369-1377.
3. Bulik-Sullivan B, Finucane HK, Anttila V, et al. An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015;47(11):1236-1241.
4. Morrison J, Knoblauch N, Marcus JH, et al. Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics. Nat Genet 2020;52:740–747.
5. Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007;81:559–575.
6. Stuart T, Butler A, Hoffman P, et al. Comprehensive Integration of Single-Cell Data. Cell 2019;177:1888-1902.e21.
7. Finucane HK, Bulik-Sullivan B, Gusev A, et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat Genet 2015;47:1228–1235.
8. Freuer D, Linseisen J, Meisinger C. Asthma and the risk of gastrointestinal disorders: a Mendelian randomization study. BMC Med 2022;20:82.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction

Immune checkpoint inhibitors (ICIs) are now considered the first-line treatment for advanced melanoma and non-melanoma skin cancers. One of the most commonly reported adverse events is checkpoint inhibitor-induced liver injury (ChILI), which occurs in approximately 10% of patients. For those who develop ChILI, it remains uncertain whether permanent discontinuation of the drug is necessary or if treatment can be safely resumed after a temporary pause, either with the same agent or with a different class of ICI. This report shares our center's experience with ChILI in patients receiving care for skin neoplasms at a tertiary-level facility.

Aims & Methods

This study aimed to analyse the prevalence of ChILI among patients treated with ICIs for skin cancers at our center. We included retrospectively all consecutive patients admitted to our facility who received ICI therapy for advanced melanoma or non-melanoma skin cancer between June 2016 and April 2024. The diagnosis and severity of ChILI were evaluated using the CTCAE v5.0 criteria, and the type of liver injury was classified based on international guidelines. Liver function tests (LFTs) were collected at baseline, after three treatment cycles, and at the time of suspected ChILI onset. Data on ChILI management and outcomes were also collected.

Results

We enrolled 111 patients (32.4% female, median age 75 years), including 70 patients (63.1%) with advanced melanoma and 41 (36.9%) with locally advanced or metastatic cutaneous squamous cell carcinoma. Among them, 3 patients (2.7%) received first-line therapy with anti-CTLA-4, 106 (95.5%) with anti-PD-1, and 2 (1.8%) were treated with a combination of both. The median duration of therapy was 10 months (IQR 5–21). ChILI developed in 8 patients (7.2%) after a median of 14 treatment cycles (IQR 7–20). According to the CTCAE severity scale, one case was grade 2, three were grade 3, and four were grade 4.
Among those who developed ChILI, 3 patients tested positive for anti-nuclear antibodies (ANA), 1 had a positive extractable nuclear antigen (ENA) test, and 2 had a known autoimmune disorder prior to initiating ICI therapy. All patients discontinued ICIs upon ChILI onset. Liver function tests normalized spontaneously in 4 patients, while 4 required corticosteroid treatment. Four patients underwent drug rechallenge, and only one of them received a new class of ICI.
Regarding extrahepatic adverse events, ChILI patients more frequently exhibited diarrhea and dermatological manifestations such as papular or bullous rashes (37.5% and 50%, respectively), with a significantly higher prevalence compared to patients without ChILI (7.8% and 15.4%, respectively; p < 0.05). No significant differences in liver function test results were observed at baseline or after the third infusion between patients who developed ChILI and those who did not (p > 0.05).

Conclusion

Our study confirms the occurrence of liver toxicity associated with ICI therapy in cancer patients, with an incidence rate consistent with current international literature. The median time to ChILI onset—typically after multiple treatment cycles—supports the hypothesis of an indirect, immune-mediated mechanism rather than a direct toxic effect on the liver. Notably, we found that ChILI is often preceded by dermatological and/or gastrointestinal adverse events.
Although based on a limited patient cohort, this observation may serve as an important clinical signal, helping physicians to anticipate ChILI, intervene earlier, prevent progression to more severe presentations, and initiate appropriate management promptly.

Clinical Case Summary

A 48-year-old man was diagnosed with a 2.0x2.5 cm protrusion in the descending duodenal bulb (A). Endoscopic ultrasonography and CT scans confirmed the mass arising from the muscularis propria (B). After discussion, we chose endoscopic full-thickness resection (EFTR). A dual knife was used to incise the mucosal cap covering the lesion and gradually separating it from the muscularis propria. After resection, there is a significant full-thickness defect of approximately 1.5x2.5 cm (C). Attempts to close the wound using titanium clips were unsuccessful due to the wound's large size. The narrow space and tender wall also complicated the use of nylon ropes and titanium clips, which increased the risk of clip detachment or mucosal injury. To overcome this challenge, we innovatively used a long transparent cap from a ligation device to enhance suction. By suctioning both sides of the mucosa into the cap, we were able to manipulate the clips with enhanced suction to achieve complete closure. A thorough examination and insufflation confirmed satisfactory wound closure and luminal dilation (D) (Video). The patient was discharged five days postoperatively without any adverse events. Histopathological examination confirmed complete resection of a low-risk GIST.

Introduction

Loss of skeletal muscle mass (SMM), one of the hallmarks in the diagnosis of sarcopenia, is a frequent condition in patients with inflammatory bowel disease (IBD) and it is a negative predictor of disability and poor clinical outcomes.¹ Despite its clinical relevance, its diagnosis remains challenging due to limited access to standard methods like dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), and magnetic resonance imaging (MRI). More practical alternative, such as bioelectrical impedance analysis (BIA) and ultrasound (US), should be investigated.^2-4

Aims & Methods

This study aims to evaluate the feasibility, reproducibility, and diagnostic accuracy of US measurement of psoas muscle thickness compared to BIA in assessing SMM in IBD patients.
US psoas muscle thickness adjusted for body mass index (BMI) was compared with BIA-derived SMM normalized to squared height. Feasibility and reproducibility between the two investigators were evaluated by intra-class correlation coefficient (ICC). SMM normalized to squared height and US thickness adjusted for BMI values were compared with Pearson’s test. Results were considered significant with a p value <0.05. The diagnostic accuracy of US psoas muscle thickness measurement in comparison to SMM with BIA was assessed by calculating sensitivity (Sens), specificity (Spec), positive and negative likelihood ratios (LR+, LR-) with their 95% confidence intervals (95% CI). This study was approved by the local Ethics Committee (no. 0049113).

Results

A total of 86 consecutive patients with IBD were prospectively enrolled, including 67.4% with CD and 32.6% with UC. The cohort had a male predominance (68.6%), with a mean age of 50.4 ± 17 years and a mean BMI of 23.68 ± 3.73 kg/m². US assessment of psoas muscle thickness was feasible in all patients. Inter-operator reproducibility was excellent with an ICC of 0.951. A significant positive correlation (r = 0.54, p < 0.0001) was observed between the US-derived psoas thickness adjusted for BMI and SMM as measured by BIA and normalized to squared height. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUROC) of 0.753 for men and 0.758 for women. Sex-specific cut-offs of psoas thickness × BMI were determined (≤108.18 cm·kg/m² for men, ≤66.9 cm·kg/m² for women), yielding sensitivities of 93.5% and 78.5% and specificities of 53.6% and 69.2%, respectively. Low SMM was defined according to BIA-based thresholds normalized to height squared, with cut-offs of <6.68 kg/m² for females and <8.97 kg/m² for males, as proposed by Peine et al. ⁵

Table 1. Ultrasound psoas thickness compared to skeletal muscle mass values at bioelectrical impedance analysis

Conclusion

US measurement of psoas muscle thickness is a feasible, low-cost, non-invasive and reproducible method for evaluating SMM in IBD patients. It shows promising diagnostic accuracy compared to BIA and, since the psoas muscle is a key anatomical landmark for evaluating the terminal ileum, it could be used as a practical first-line screening tool for sarcopenia especially in routine bowel US. Further prospective studies are needed to refine cut-off values, validate findings in diverse populations, and assess the long-term prognostic implications of this technique within the framework of personalized IBD management.

References

1. Nishikawa, H. et al. Inflammatory bowel disease and sarcopenia: Its mechanism and clinical importance. Journal of Clinical Medicine vol. 10 Preprint at https://doi.org/10.3390/jcm10184214 (2021).
2. Oshima, Y., Shiga, T., Namba, H. & Kuno, S. Estimation of whole-body skeletal muscle mass by bioelectrical impedance analysis in the standing position. Obes Res Clin Pract 4, (2010).
3. Smith, R. L., Taylor, K. M., Friedman, A. B., Gibson, R. N. & Gibson, P. R. Systematic Review: Clinical Utility of Gastrointestinal Ultrasound in the Diagnosis, Assessment and Management of Patients with Ulcerative Colitis. Journal of Crohn’s and Colitis vol. 14 Preprint at https://doi.org/10.1093/ecco-jcc/jjz163 (2020).
4. Mulinacci, G. et al. P466 Ultrasound muscle assessment for sarcopenia screening in patients with Inflammatory Bowel Disease: A prospective study (SarcUS-IBD). J Crohns Colitis 18, (2024)
5. Peine, S. et al. Generation of normal ranges for measures of body composition in adults based on bioelectrical impedance analysis using the seca mBCA. Int J Body Compos Res 11, (2013).

Disclosure

No conflict of interest