Introduction

There are three main concepts in colorectal carcinogenesis. The first is the well-known “adenoma-carcinoma sequence”, while the second is the “saw-tooth lesion pathway”. In this concept, serrated lesions transform into early carcinomas. The third concept is the “de novo” pathway, in which early carcinomas can develop even in the absence of an adenoma. In this pathway, the cancer is thought to arise directly from the normal epithelium, rather than from an adenoma, and the cancer tends to progress at a faster rate and with a higher grade of malignancy. For diagnosing colorectal cancer, magnified endoscopy, specifically the Pit pattern classification, has proved to be useful. Recently, the endoscopic examination (EC classification) has been developed, and now not only structural atypia but also cellular atypia can be observed in vivo.
In this study, we aimed to clarify the endoscopic characteristics of colorectal cancer and demonstrate the usefulness of pit pattern classification and EC classification. Our study focused mainly on colorectal cancer that is considered to arise through the "de novo" pathway.

Aims & Methods

From April 2001 to December 2022, a total of 45,419 colorectal neoplasms, excluding advanced cancer that were resected endoscopically or surgically at Showa University Northern Yokohama Hospital. Among them, 37,098 were low-grade dysplasia, 6,802 were advanced dysplasia, and 1,519 cases were submucosal invasive carcinoma. In this study, we investigated the characteristics of depressed carcinomas with respect to Pit patterns and EC classification.

Results

Of all the T1 colorectal cancers, depressed lesions accounted for 61.4% (324/528). In contrast, flat and protruding lesions accounted for only 2.9% (575/19,578) and 2.7% (673/25,313) of T1 cancers, respectively. Flat (95.1% (18,619/19,578)) and raised (94.2% (23,844/25,313)) lesions showed mostly type IIIL and type IV pit patterns corresponding to adenomas. Among depressed lesions, 92.2% (486/528) were types IIIS, VI, and VN, corresponding to adenocarcinoma in pit pattern classification. On endoscopy, most of the flat or protruding lesions corresponded to adenomas and were classified as type EC2 in the EC classification, whereas the depressed lesions were mostly classified as EC3a and EC3b (91.2%), indicating invasive carcinoma according to the EC classification.

Conclusion

This study demonstrates that depressed colorectal cancer is prone to invade the submucosa, highlighting the need for magnifying endoscopy and endoscopy, regardless of the size of the lesion. Nonetheless, detecting this type of colorectal cancer can present a significant challenge. Thus, greater attention must be devoted to the morphological characteristics of depressed colorectal cancer during routine colonoscopy.

Introduction

Pancreatic steatosis (PS) has been increasingly recognized and associated with some relevant metabolic implications. However, data on its correlation with exocrine pancreatic function remain limited. We conducted a systematic review and meta-analysis to evaluate whether PS is associated with exocrine pancreatic insufficiency (EPI).

Aims & Methods

This study aimed to investigate whether imaging-detected PS is related to exocrine pancreatic dysfunction, assessed by fecal elastase-1 (FE-1) levels. We searched PubMed, EMBASE, and Cochrane Central for studies including adults with and without PS identified on imaging, and reporting FE-1 concentrations. Data were pooled using random-effects models.

Results

Three studies evaluating a total of 1,864 patients were included. Fecal elastase levels were significantly lower in patients with PS compared to controls, indicating worse exocrine pancreatic function in this group (MD -199.78; 95% CI -303.66 to -95.91; p < 0.05; I² = 97%). Moreover, PS was associated with a significantly increased risk of exocrine pancreatic insufficiency (RR 3.13; 95% CI 1.17–8.40; p = 0.023; I² = 81%), reinforcing the link between fat accumulation in the pancreas and impaired exocrine function.

Conclusion

This meta-analysis demonstrates a significant association between PS and impaired pancreatic exocrine function, compared to individuals without known pancreas disease. These findings underscore the importance of a comprehensive metabolic assessment in patients with PS, given its potential role in pancreatic dysfunction.

Introduction

Recurrent abdominal pain is the predominant symptom of chronic pancreatitis (CP), contributing to significant morbidity and reduced quality of life. Medical management includes analgesics, antioxidants, neuromodulators, and pancreatic enzyme replacement therapy (PERT). While PERT is used for pancreatic exocrine insufficiency (PEI), it is also thought to reduce pain by suppressing pancreatic secretion via negative feedback. However, previous meta-analysis did not show pain reduction, though subgroup analysis suggested potential pain relief with non-enteric (NE) coated enzymes1. Unlike currently available enteric-coated formulations, high in lipase but low in proteas, non-enteric coated enzymes with high protease content dissolve rapidly and may more effectively suppress cholecystokinin-mediated pancreatic stimulation, potentially improving pain outcomes.

Aims & Methods

To primarily assess the effect of a high-protease, non-enteric-coated pancreatic enzyme preparation on pain in patients with painful chronic pancreatitis. The study was registered under ClinicalTrials.gov (NCT05042284).
We conducted a randomized, double-blind, placebo-controlled trial where we randomly assigned participants to a high protease (30,000 U)-containing, non-enteric-coated enzyme preparation (n=54) and a placebo (n=53) group. The study duration was 24 weeks. Patients with painful CP (per Mayo Clinic criteria) with chronic pain were enrolled. The primary outcome was to see a difference in mean Izbicki pain score at 12 and 24 weeks and a change in pain scores (VAS 0-10) using pain diaries. Secondary outcomes were changes in the number of painful days, analgesic requirements, patient’s global impression of change (PGIC), quality of life, and adverse effects. Weekly pain data were collated. Repeated measures, linear, and mixed-effects models were used to analyze the primary outcome. Analysis was intention-to-treat.

Results

107 out of 256 screened patients fulfilled enrollment criteria. The mean age was comparable between groups (35.1±10.6 vs. 33.6±12.3 years; p=0.51), and baseline characteristics were similar. The primary outcome using mixed model analysis showed no significant differences in the change in Izbicki pain scores between the two groups at 12 and 24 weeks (Table: Results). The mean difference in VAS pain score was -3.7(95%CI: -4.3to-3.1) in enzyme group vs. -3.5(95%CI: -4.2to-2.9) in placebo group (p=0.64) at 12 weeks. The changes were -4.2(95%CI: -4.7to-3.6) vs. -4.1(95%CI: -4.7to-3.5), respectively (p=0.79), at 24 weeks indicating no significant difference. The median number of painful days was also similar, at 12 weeks, 16 (IQR: 9–35) in the enzyme group vs. 16 (IQR: 4–36.5) in placebo (p=0.31); at 24 weeks, 3(IQR: 0–8.5) vs. 3(IQR: 0–7)(p=0.30) respectively. Analgesic use was higher in the enzyme group at 12 weeks (45(83.3%) vs. 37(69.8%); p=0.11) and 24 weeks (42(77.8%) vs. 35(66%); p=0.20). Differences in the change in global health status, quality of life, PGIC, and adverse effects at both time points were also non-significant.

Conclusion

Despite the high protease content, Non-enteric coated enzyme preparations did not improve pain and quality of life in patients with painful chronic pancreatitis. Further RCTs are needed to evaluate benefits in distinct subgroups.

References

1. Yaghoobi, Mohammad, Julia McNabb-Baltar, Raheleh Bijarchi, and Peter B. Cotton. “Pancreatic Enzyme Supplements Are Not Effective for Relieving Abdominal Pain in Patients with Chronic Pancreatitis: Meta-Analysis and Systematic Review of Randomized Controlled Trials.” Canadian Journal of Gastroenterology and Hepatology. Doi: https://doi.org/10.1155/2016/8541839

Introduction

Acute pancreatitis (AP) is a common cause of acute hospital admissions, with the potential for severe acute complications, progression to chronic pancreatitis and recurrent episodes. A first presentation leads to investigations to identify a cause, including serum blood tests and transabdominal ultrasound. Following these investigations, a significant minority of patients have no clear cause for pancreatitis. Endoscopic ultrasonography (EUS) can identify aetiologies of AP, and direct intervention to reduce recurrence. The goal of this study was to determine the diagnostic yield of EUS and the impact of subsequent biliary intervention on recurrence of AP.

Aims & Methods

This was a retrospective service evaluation of EUS referrals to a regional referral centre in the UK from January 2015 to December 2019. Demographics, symptoms, liver blood tests, non-invasive imaging, EUS records and outcomes were reviewed. A EUS was labelled as diagnostic if findings were identified which explained the cause for pancreatitis that had not been explained with other investigations. Symptom resolution was defined as no further episodes of acute pancreatitis or abdominal pain requiring investigation, imaging, or presentation to secondary care during the follow-up period. Statistical significance for the difference between proportions was calculated using chi-squared tests.­­­­­­­­­­

Results

Ninety-seven patients were included in the study. The median age of the cohort was 58 (range 18-88) years. 55 (57%) patients were male. 22/97 (23%) patients had previously had a cholecystectomy. 41/97 (42%) had abnormal liver blood tests at the time of referral. Three patients had no non-invasive imaging. 27/97 (28%) had one of either transabdominal ultrasound, MRCP or CT, 63/97 (65%) had two tests and 4/97 (4%) had all three. 5 (5%) patients previously had a non-diagnostic EUS.
72/97 (74%) EUS were diagnostic. Findings included gallstones (n=15), gallbladder microlithiasis/sludge (n=51), bile duct stones (n=13), bile duct microlithiasis/sludge (n=11), chronic pancreatitis (n=7) and a pancreatic mass (n=1) which was later diagnosed as a pancreatic adenocarcinoma.
65 patients had a biliary aetiology for their pancreatitis which was amenable to treatment. Of these, 12 had subsequent ERCP, 7 had ERCP and cholecystectomy, 33 had a cholecystectomy and 13 were treated conservatively. Recurrent pancreatitis occurred in 12/52 (23%) patients who had treatment for a biliary aetiology of their pancreatitis compared with 8/13 (75%; p<0.01) of patients who were managed conservatively despite a biliary aetiology for pancreatitis, 8/32 (25%; p=0.84) of patients with a diagnostic EUS with a finding not amenable to treatment or a non-diagnostic EUS experienced further episodes. One patient died from complications related to acute pancreatitis and was not included in this analysis. Median duration of follow-up was 51 months (range 32-80 months).

Conclusion

In our cohort of patients referred for EUS for unexplained acute pancreatitis, EUS had a high diagnostic yield. A lower proportion of patients had a biliary aetiology for their pancreatitis that was amenable to intervention with either ERCP, cholecystectomy or both procedures; these patients experienced fewer episodes of recurrent acute pancreatitis than those managed conservatively. This supports the use of EUS in patients with acute pancreatitis with no cause identified with non-invasive imaging.

Introduction

Response rates to the Low FODMAP Diet (LFD) in IBS vary and predictors of benefit remain poorly defined. While several studies from Western populations have identified microbial signatures linked to response, data from Asian cohorts remain limited.

Aims & Methods

This study aims to identify microbial predictors and longitudinal microbiome shifts in Asian IBS-D patients consuming a LFD. We recruited 20 adult Asian patients with IBS-D diagnosed according to the ROME-IV criteria. All subjects received LFD dietary advice from a dietitian at initiation and were followed-up for a total of 28-days. Clinical response was assessed by a ≥50-point improvement in the IBS Symptom Severity Score (IBS-SSS) from Day 0 (baseline) as compared to follow-up at Day 28. Stool samples were collected at baseline, Day 14, and Day 28. Microbial DNA was extracted using bead-beating and Qiagen PowerFecal kits, and the V3–V4 region of the 16S rRNA gene was amplified and sequenced on the Illumina MiSeq platform. Bioinformatic processing included denoising with DADA2, taxonomic assignment using the SILVA 138 database, and rarefaction to even sequencing depth. Microbiome metrics included alpha diversity (Shannon and Simpson), beta diversity (Bray-Curtis PCoA with PERMANOVA), and differential abundance testing with DESeq2.

Results

By Day 28, 11 of 20 patients (55%) achieved clinical response, with a median IBS-SSS reduction of 172 points (IQR: 88–248), compared to 24 points in non-responders (IQR: −11 to 55; p=0.003). Alpha diversity was not significantly different between groups, but responders exhibited a trend toward higher Shannon and Simpson diversity at baseline. Beta diversity analysis using Bray-Curtis dissimilarity revealed partial clustering by responder status (PERMANOVA p=0.06), and PCoA plots showed individual-specific shifts in community structure across time, indicating that the LFD induces personalized microbiome trajectories.
At baseline, responders had significantly higher relative abundances of butyrate-producing and anti-inflammatory genera, including Ruminococcus, Blautia, Eubacterium siraeum, and Bifidobacterium bifidum (adjusted p<0.05). These findings are consistent with prior reports, including Bennet et al. (2018) and Vervier et al. (2022), where such taxa were part of a “health-like” IBS-P (pathogen-enriched) to IBS-H (health-like) axis. The enrichment of Blautia and Ruminococcus is particularly noteworthy as these are established butyrate producers involved in maintaining colonic barrier function and reducing visceral hypersensitivity. By Day 28, differential abundance analysis revealed that responders exhibited increases in Ruminococcus bicirculans, Parabacteroides gordonii, and Weissella cibaria. In contrast, non-responders showed persistence or increases in taxa such as Tyzzerella and Olsenella, which have been associated with inflammation or IBS severity in prior studies (Chuah et al., 2024).

Conclusion

This study provides novel microbiome insights from an underrepresented Asian IBS population consuming a LFD. Despite dietary and baseline microbiota differences from Western populations, we observed remarkably consistent microbiome predictors of response, including higher baseline levels of butyrate-producing taxa and favorable microbial restructuring during the intervention. These results reinforce the reproducibility and functional relevance of microbiome predictors in IBS dietary therapy, and support microbiome profiling as a potential tool for personalized dietary guidance across a diverse global population.

References

Bennet SMP et al. Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs. Gut. 2018 May;67(5):872-881.
Vervier K et al. Two microbiota subtypes identified in irritable bowel syndrome with distinct responses to the low FODMAP diet. Gut. 2022 Sep;71(9):1821-1830.
Chuah KH, Mahadeva S. Can we predict who will respond to a low-FODMAP diet in irritable bowel syndrome? J Gastroenterol Hepatol. 2024 Feb;39(2):217-218. ​

Introduction

Endoscopic ultrasound-guided gallbladder drainage is usually reserved for high surgical risk patients. The procedure was usually performed under deep sedation to ensure the best tolerability for the patient and facilitate the endoscopist’s performance.
However, many of them showed a high-risk even for deep sedation.

Aims & Methods

Our aim was to evaluate the safety and efficacy of EUS-GBD under conscious sedation (CS).
All consecutive EUS-GBD under CS performed in our hospital were prospectively enrolled from January 2020 to December 2022.
Patient characteristics, type and dosage of anesthetic drug administered (Fentanyl (FNT), Pethidine (PTD) or Benzodiazepine (BZD)), size of lumen-apposing-metal-stent (LAMS), gallbladder (GB) access, technical success, clinical success, early and late adverse events (AEs) rate were evaluated. Safety was defined as AEs occurrence. The efficacy of EUS-GBD was expressed as technical and clinical success. We defined as “conscious sedation” a drug-induced depression of consciousness during which patients respond to verbal commands or react to touch. Breathing remains intact and no support is needed.

Results

A total of 49 patients (41.7% male, mean age 82,9±10 years-old) underwent EUS-GBD under in our Unit. Among all the 49 EUS-GBD in CS, 47 (95.9%) were indicated as treatment for acute cholecystitis in high-surgical-risk patients and 2 (4.1%) as rescue-strategy after ERCP fail.
In 45 (91.8%) EUS-GBD a 10x10mm LAMS was deployed, in 3 (6.2%) procedures a 15x10mm and in 1 (2%) an 8x8mm LAMS. GB was accessed from the duodenum in 68.8% of cases.
A combination of PTD+BZD was administered in 29 (59.2%) EUS-GBD, while 18 (36.7%) procedures were performed under FNT+BZD. Only 2 (4.1%) EUS-GBD were performed only under BZD.
Mean FNT, PTD, BZD dose were 50(±11.5) mcg, 38.4(±25.6) mg and 4(±1.5) mg, respectively.
Technical success of EUS-GBD under CS was 97.9%. In one procedure the distal flange of the LAMS did not open due to LAMS malfunction. The clinical success of EUS-GBD under CS was 97.9% since in one procedure there was not a decrease of inflammatory, cytolysis and cholestasis indices. Only in 1 (2%) EUS-GBD an early AE was reported. No late AEs were described.
The statistical analysis showed that the administration of a combination of fentanyl and benzodiazepine or a combination of pethidine and benzodiazepines or the administration of only benzodiazepines affected neither technical nor clinical success, nor AEs rate (Table 1).

Conclusion

EUS-GBD under CS was a safe procedure with a low AEs rate.
The administration of FNT+BZD, PTD+BZD or BZD alone did not affect procedure outcome.

Introduction

Measurement of the size of colorectal polyps during colonoscopy is carried out mainly by visual estimation. We developed a novel polyp size measurement system (Poseidon) based on artificial intelligence that uses the auxiliary water jet as a measurement reference.

Aims & Methods

Visual estimation, biopsy forceps measurement, and Poseidon were compared using a CT colonography-based silicon colon model with 28 polyps of known size. Four experienced endoscopists estimated polyp size visually and with biopsy forceps. The endoscopists took images of each polyp with the water jet in its proximity. These images were then analyzed by Poseidon to measure the size of the polyp.
Additionally, the Poseidon measurements were compared to visual size estimates of 29 colorectal polyps examined during clinical routine.

Results

In the silicone colon model, the visual estimation had the largest median percent error (PE) of 25.2% (interquartile range (IQR: Q1, Q3): 11.8, 43.1), followed by the biopsy forceps measurements with a median PE of 20% (IQR: 9.1, 34.3). Poseidon had a significantly lower median PE of 7.4% (IQR: 3, 15.7, p<0.001) than the other two methods.
At routine colonoscopies, Poseidon had a significantly lower median PE (7.7%; IQR: 2.7, 12.6) than the visual estimation (22.1%; IQR: 12.4, 34.1, p<0.001).

Conclusion

In this work, we present a novel method to measure the size of colorectal polyps, which has a significantly higher accuracy than other common polyp sizing methods.