Introduction

With the rising incidence of early-onset colorectal cancer (EOCRC) in developed countries, it is crucial to improve our understanding of typical signs and symptoms to enable an earlier diagnosis.

Aims & Methods

The aim of this study was to examine the signs, symptoms, tests and prescriptions recorded during two distinct periods prior to the diagnosis of EOCRC: within one month and within one year before diagnosis. Our objective was to identify potential consistent markers that could support earlier diagnosis.
We analysed longitudinal cohort data from three real-world databases from the UK (CPRD GOLD, AURUM, and THINK UK) focusing on patients diagnosed with EOCRC at age 18-49. We performed a large-scale characterization in a random sample of 1,000 individuals with EOCRC (we extracted the signs and symptoms, tests, and prescriptions recorded in patient records). For each, we computed the Relative Risk Increase (RRI) between EOCRC patients and age- and sex-matched controls.

Results

We identified 16,772 cases of EOCRC. In the year leading up to diagnosis, rectal haemorrhage was recorded in 11.5% of EOCRC cases (RRI of 21.2), based on data from CPRD-GOLD. Similarly, abdominal pain and constipation were recorded in 10.7% (RRI 8.4) and 4.8% (RRI 8) of EOCRC cases, based on data from CPRD-Aurum and THIN UK, respectively. Irritable bowel disease (IBS) and iron deficiency anaemia were diagnosed in 4.5% (RRI 6.2) and 4.4% (RRI 4.3), based on data from CPRD-GOLD and CPRD-Aurum respectively. Laboratory tests related to anaemia were more commonly requested among EOCRC patients. For example, serum ferritin was tested in 15.8% of the patients based on data from CPRD-GOLD (RRI of 3.6), and 22.7% based on data from THIN UK (RRI of 2.6). Tissue transglutaminase IgA (for coeliac disease diagnosis) was measured in 6.6% of the patients (RRI 11.8) based on data from CPRD-Aurum. Prescriptions for symptomatic treatments such as dibucaine, butylscopolamine, lactulose, mebeverine, and loperamide were also observed in 3.3-7.7% of cases (RRI of 4.8 to 11.8) across the datasets. Surgical referrals were also more common among EOCRC cases (RRI of 1.2 to 5.6) in the year leading up to diagnosis, with absolute percentages ranging from 4.7% to 6.6%, based on both CPRD databases. This was primarily driven by rectal cases. All these trends were consistent across databases.
In the month preceding diagnosis, clinical activity was dominated by codes related to blood test parameters across all databases.

Conclusion

Signs and symptoms potentially related to CRC were often recorded during the year preceding diagnosis. However, clinical suspicion of CRC remained low in patients under 50, with symptoms frequently attributed to alterative (and potentially co-existing) diagnoses such as haemorrhoids or coeliac disease. While individual symptoms may not always raise clinical concern, combinations of signs, symptoms, and test results could be more informative. Future work should focus on developing predictive tools -potentially incorporating artificial intelligence- to identify individuals at risk based on patterns of clinical features. Such tools could improve early detection and guide timely diagnostic strategies for EOCRC.

References

1) Siegel RL, Jakubowski CD, Fedewa SA, Davis A, Azad NS. Colorectal Cancer in the Young: Epidemiology, Prevention, Management. Am Soc Clin Oncol Educ Book. 2020 Mar;40:1-14. doi: 10.1200/EDBK_279901. PMID: 32315236.
2) Dernie F, Corby G, Robinson A, Bezer J, Mercade-Besora N, Griffier R, Verdy G, Leis A, Ramirez-Anguita JM, Mayer MA, Brash JT, Seager S, Parry R, Jodicke A, Duarte-Salles T, Rijnbeek PR, Verhamme K, Pacurariu A, Morales D, Pinheiro L, Prieto-Alhambra D, Prats-Uribe A. Standardised and Reproducible Phenotyping Using Distributed Analytics and Tools in the Data Analysis and Real World Interrogation Network (DARWIN EU). Pharmacoepidemiol Drug Saf. 2024 Nov;33(11):e70042. doi: 10.1002/pds.70042. PMID: 39532529.

Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and eosinophilic inflammation of the esophageal mucosa. In this study, we investigated the bacterial flora in saliva and esophageal mucus in patients with EoE and examined the relationship between EoE disease activity and mucosal cytokine expression.

Aims & Methods

Cases consisted of patients with active and inactive EoE (A-EoE and I-EoE, respectively). A-EoE was defined as a peak eosinophil count > 15/high-power field, according to the 2025 consensus guidelines. Saliva samples were collected from the patients before the endoscopic examination. Brushing samples were collected from the distal esophagus of patients with EoE during endoscopic procedures. The degree of EoE inflammation was assessed using the EoE endoscopic reference score (EREFS). The samples were profiled using the Illumina MiSeq platform. The V3–V4 regions of the 16S rRNA gene (460 bp) were amplified by using tailed PCR.

Results

Fifty-nine patients were enrolled, including 8 with I-EoE, 17 with A-EoE, and 28 non-EoE controls. Major bacterial genera, such as Streptococcus, Prevotella, Veillonella, and Alloprevotera, were detected in both the oral cavity and esophagus. Compared with the control group, the active EoE group had significantly more Prevotella spp. in the saliva and esophageal mucosa. Conversely, significantly fewer Neisseria spp. were found in the saliva and Streptococcus spp. in the esophageal mucosa of patients with active EoE. The EREFS of EoE and Streptococcus were inversely correlated.

Conclusion

In this study, we clarified the characteristics of the bacterial flora in the saliva and esophageal mucosa of patients with eosinophilic esophagitis.

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

Contemporary studies suggest there are racial disparities in the outcomes of acute presentations. This study aimed to investigate the impact of sex and race on the management and outcomes of patients presenting with upper gastrointestinal bleeding (UGIB).

Aims & Methods

Using International Classification of Diseases 10th Revision Codes, all adults >18 admitted from 2016–2020 with a discharge diagnosis of UGIB were extracted from the National Inpatient Sample.

Results

In over 900,000 hospitalisations for UGIB, 69.4%, 14.1%, 9.6%, 3.6%, 0.9% and 2.4% were for admissions in white, black, Hispanic, Asian/pacific islander, native American and ‘other’ patients respectively. Comorbidity burden varied between racial groups (p<0.001). White patients had higher crude rates of endoscopy, and comparable rates of surgery or interventional radiology to control blood loss, in comparison to other racial groups. Adjusted analysis revealed that black and Asian/pacific islander racial group patients had lower odds of in-hospital all cause mortality compared to white patients, but ‘other’ racial group patients had higher odds of mortality (p<0.001). There was no difference for Hispanic or native American patients. For non-variceal bleeding, these outcomes persisted. However, for variceal bleeds, there were no significant differences in outcomes between each racial group.

Conclusion

There are racial disparities in the management and outcomes of admissions for UGIB. These difference persist despite the aetiology of bleeding. Underlying reasons for differences in outcomes must be investigated to ensure improved outcomes across high-risk patient groups.

Introduction

Upper gastrointestinal bleeding (UGIB) is a major cause of mortality in the United States (US). This study aimed to investigate the contemporary trends in the management and outcomes of these patients as well as factors associated with in-hospital mortality, using national data.

Aims & Methods

The US National Inpatient Sample was queried from 2016-2020. Using International Classification of Diseases 10th Revision Codes, all adults >18 admitted with a principal discharge diagnosis of UGIB were extracted along with data about demographics, management and outcomes. Categorical variables were compared using chi-squared and expressed as percentages (%). Logistic regression was performed, adjusting for variables associated with adverse outcomes and reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Data were considered significant if p<0.001.

Results

There were 918,925 hospitalizations for UGIB in the study period. Variceal bleeding occurred in 36,050 (3.9%) of admissions. Endoscopy was performed in 451,450 (49.1%) of admissions, with 10,160 (1.1%) of admissions and 9,355 (1.0%) of admissions requiring interventional radiology and gastrointestinal surgery to control blood loss respectively. The crude rate of all-cause in-hospital mortality was 1.9%. Factors associated with death included variceal bleed (aOR 2.84 CI 2.67-3.02), age (aOR 1.03 CI 1.03-1.03), history of cancer (aOR 2.45 CI 2.35-2.56), ulcer disease (aOR 1.44 CI 1.39-1.49), chronic renal failure (aOR 1.34 CI 1.29-1.37), chronic obstructive pulmonary disease (aOR 1.29 CI 1.24-1.34), receipt of endoscopy (aOR 1.33 CI 1.29-1.38), surgery (aOR 3.92 CI 3.63-4.24) and interventional radiology (aOR 3.33 CI 3.09-3.58).

Conclusion

UGIB remains a significant cause of hospitalisation in the US. Knowledge of the contemporary trends and outcomes of this patient group is important to improve management in this at-risk patient group.

Introduction

The prevalence of adenoma in patients with positive fecal immunochemical tests (FIT) is shown to be higher. Increased adenoma detection and removal during colonoscopy have been shown to prevent CRC and interval cancers. However, there is considerable variation in the adenoma detection rate (ADR) among colonoscopies performed for FIT. We hypothesize that the ability of dye-based chromoendoscopy to stain the colorectal lesion and their borders and increase their contrast against the normal colorectal mucosa would enhance the detection of adenoma and non-polypoid colorectal neoplasms (NPCRN) in patients undergoing FIT positive colonoscopy. In this randomized control trial, we aim to compare the effectiveness of pan-colonic indigo carmine chromoendoscopy (PCC) to high-definition white light colonoscopy (WLC) in individuals undergoing colonoscopy for positive FIT test.

Aims & Methods

Patients undergoing colonoscopy after a FIT positive test were randomized 1:1 to undergo PCC or WLC. The study was conducted between January 2021 to May 2023 at the Singapore General Hospital, Singapore. Colonoscopy was performed by general and advanced endoscopists, and all received training on PCC before the study. The primary outcome was ADR between the two groups. The secondary outcomes were advanced adenoma detection rate (AADR), NPCRN detection rate, sessile serrated lesion detection rate (SSLDR), and withdrawal time between the groups. We used the two-tailed Mann–Whitney U test and Chi-squared statistics for comparison. The ethics committee approved the study, and it was registered with clinicaltrials.gov (NCT04512612)

Results

We recruited 256 patients (PCC-128; WLC-128). The mean age of the entire cohort was 66 + 8.4 years. The mean ADR was comparable between PCC and WLC (70.3% vs. 64.8%, p-0.350). Likewise, the AADR (19.5% vs. 14.8%, p-0.320], and SSLDR (6.25% vs. 1.56%, p-0.102] were similar between the two groups. We found PCC detected more diminutive adenomas (0.97% vs. 0.58%, p-0.025] and NPCRN per colonoscopy (0.35% vs. 0.17%, p-0.028). The mean withdrawal time was longer with PCC compared to WLC (13.3 min vs. 10.2 min, p-0.001). General and advanced endoscopists had no difference in performance measures for APC and NPCRN per colonoscopy.

Conclusion

The ADR in FIT-positive colonoscopy is higher, and both PCC and WLC yielded comparable results. PCC merits consideration because of its increased ability to detect NPCRNs, which are precursors for interval cancer.