Clinical Case Summary

A 69-year-old male with a history of oral anticoagulation for atrial fibrillation. He is being evaluated for intermittent melena of 6-8 month’s duration.
Laboratory tests revealed iron-deficiency anemia (microcytic and hypochromic), as well as a positive fecal occult blood test. An abdominal CT scan revealed a previously described renal pseudonodular lesion, with no other findings.
In this context, endoscopic studies were performed. Gastroscopy showed two polypoid lesions measuring approximately 20mm in the duodenal bulb, which were biopsied. Colonoscopy revealed over 20 serrated polyps, measuring 2-8mm, throughout the colon. Twelve were removed from the ascending colon, four from the sigmoid colon, and one from the rectum.
The pathological examination of the duodenal biopsies was compatible with mantle cell lymphoma, and the ascending colon polyps also showed features of this neoplasm. The sigmoid colon lesions were found to be adenomas and hyperplastic polyps.
The patient was deferred to the Hematology department, where a complete workup included serology tests, which were negative; a bone marrow biopsy and flow cytometry scan ruled out neoplastic involvement at this level; and a PET-CT scan showed FDG uptake in the ileum, as well as multiregional infradiaphragmatic lymphadenopathy, suggestive of secondary lymphoma infiltration, in addition to splenomegaly and small, nonspecific paraesophageal lymph nodes.
Given the indolent nature of the condition, a strategy of close observation without treatment was decided upon, with periodic follow-up visits and PET-CT follow-up. The patient currently remains under close observation, with no signs of progression on PET-CT, as well as improving laboratory tests.

References

Endoscopic imaging of both duodenal polyps, as well as some of the colorectal lesions.
Pathological study of the colorectal lesions, as well as immunohistochemistry.
PET-CT scan imaging showing neoplastic involvement of the ileum.

Clinical Case Summary

We present the case of an 82-year-old patient with a history of ischaemic stroke, diabetes and atrial fibrillation who was referred to Gastroenterology for multiple colonic polyps, including a lateral spreading tumour (LST) in the splenic flexure. The patient underwent total colonoscopy for endoscopic mucosal resection (EMR), identifying a non-granular pseudodepressed LST (Paris 0-Is+IIa+IIc) 30mm in size, with a central depression with irregular crypt pattern (JNET 2B) and a peripheral component with a regular crypt pattern (JNET 2A). An attempt was made to inject the submucosa with inadequate elevation, so EMR was not performed. The remaining polyps were removed without complications. A multidisciplinary team discussion decided on advanced endoscopic resection. The patient was submitted to colonoscopy, performing piecemeal EMR of the peripheral component and endoscopic full thickness resection (EFTR) of the central non-lifting component. There were no complications from the procedure. Histology of the specimen identified tubular adenocarcinoma, well differentiated, without tumor budding, perineural nor lymphovascular invasion and Kikuchi classification was sm1. The margin was free of neoplasia. After further discussion with the multidisciplinary team, he was considered curative and was proposed for endoscopic surveillance.
We present this case to illustrate the hybrid technique of EMR with EFTR as an effective alternative for the complete resection of large complex adenomas with non-lifting component, since R0 resection with EFTR is hard to achieve for lesions larger than 20mm. In our case, hybrid EMR and EFTR enabled curative endoscopic resection of an adenocarcinoma.

References

The case is illustrated with images and videos of the endoscopic procedure and histopathological analyses.

Introduction

Achieving histologic remission leads to improved outcomes for patients with ulcerative colitis (UC). However, predictors of histologic remission remain poorly defined. We aimed to identify patient and disease characteristics that predicted histologic remission in patients with UC.

Aims & Methods

The phase IV Vedolizumab Immunomodulator Enforced Withdrawal Study (VIEWS) prospectively recruited UC patients in steroid-free clinical remission on vedolizumab (VED) 300mg intravenously 8-weekly and a thiopurine. All patients were in endoscopic improvement (Mayo endoscopic score 0 or 1) at baseline, with or without histologic activity. Histologic remission was defined as Nancy index=0, with central reading by a blinded gastrointestinal pathologist. Clinical variables (age, sex, disease duration, smoking status, extent of UC, concomitant medications, anti-TNF exposure) and biochemical variables (serum VED trough level, faecal calprotectin, TGN, albumin) were analysed. Odds ratios (ORs) with 95% confidence intervals (CI) were reported. Multivariate logistic regression models were performed to identify predictive factors of histologic remission at baseline. Covariates with P<0.05 were deemed statistically significant (IBM SPSS Statistics, version 30).

Results

Of 62 consecutively recruited UC patients, 54 patients had baseline histologic assessment and 76% (n=41) were in histologic remission. Baseline demographics included median age 43 years (IQR:27-60), female 44% (n=24), non-smokers 78% (n=42), ex-smokers 15% (n=8), median disease duration was 6.5 years (IQR:3-11) and 83% (n=45) were anti-TNF naïve. Current smokers (n=3) were excluded from analysis due to low numbers. Univariate predictors of histologic remission at baseline included age (OR: 0.96 [95%CI:0.93-0.99], P=0.04), non-smoking versus ex-smoking (OR: 14.93 [95%CI:2.49-90.91], P<0.001) and anti-TNF naïve (OR: 5.78 [95%CI:1.26-26.32], P=0.03). On multivariate analysis, only non-smoking versus ex-smoking predicted for histologic remission (OR: 19.65 [95%CI:1.37-281.93], P=0.03) (Table 1).

Table 1. Factors associated with histological remission at VIEWS study entry
OR, odds ratio; CI, confidence interval; UC, ulcerative colitis; TNF, tumour-necrosis factor; TGN, thioguanine; μg, microgram; mL, millilitre; g, gram.

Conclusion

Non-smoking is more likely to be associated with histologic remission than ex-smoking in UC. Ex-smokers may have worse outcomes than non-smokers in UC.

Disclosure

A. Pudipeddi has received speaker fees from AbbVie, Dr Falk Pharma, Janssen, Takeda, Pfizer and Ferring, and has served on an advisory board for AbbVie. S. Paramsothy has received speaking and consulting fees from AbbVie, Janssen and Takeda. R.W. Leong advisory board membership AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda, and research grants: Joanna Tiddy USYD, McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Medical Research Future Fund of Australia.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is one of the most common chronic liver conditions worldwide. Alterations in gut microbiota composition and impaired gut barrier function are increasingly recognized as key contributors to MASLD development and progression.

Aims & Methods

The aim was to assess the gut microbiota composition in patients with MASLD and to evaluate its role in the development and progression of the disease. The study included 152 patients diagnosed with MASLD (mean age 46.5±0.89 years) and 150 control subjects without liver pathology (mean age 48.36±0.97 years). MASLD was diagnosed using liver ultrasound, hepatorenal index evaluation, and identification of cardiometabolic risk factors. Gut microbiota composition was analyzed by quantitative real-time PCR, focusing on the abundance of Firmicutes, Actinobacteria, Bacteroidetes, and Akkermansia muciniphila.

Results

Patients with MASLD demonstrated significantly increased levels of Firmicutes (50.3±2.46%) and Actinobacteria (15.34±2.87%) compared to controls (25.17±1.51% and 10.9±1.87%, respectively), alongside a higher Firmicutes/Bacteroides (F/B) index (5.02±2.61 vs. 2.1±1.74). The presence of Akkermansia muciniphila was substantially reduced in MASLD patients (33%) compared to the control group (63%). Positive correlations were found between Actinobacteria levels and the F/B index (r=0.75, p≤0.05), as well as between the F/B index and triglyceride levels (r=0.68, p≤0.05). A negative correlation was observed between the presence of Akkermansia muciniphila and MASLD diagnosis (r=–0.69, p≤0.05).

Conclusion

MASLD patients show profound dysbiosis characterized by an increase in Firmicutes and Actinobacteria, an elevated F/B index, and a reduction in Akkermansia muciniphila abundance, indicating compromised gut barrier integrity. Akkermansia muciniphila may play a protective role against MASLD progression, highlighting the potential of microbiome-targeted therapies to prevent or mitigate disease development.

Introduction

With the introduction of direct-antiviral medication (DAAs), eradication of HCV infection is considered now an achievable goal. While people with history of drug use (PWHD) form the most common population at risk for the infection, in Greece historically there has been a significant proportion of patients arising from the general population with no prior drug use. These two different subgroups exhibit different characteristics, that may be pertinent in the management of HCV infection and long-term follow up.

Aims & Methods

The aim of this study was to identify potential differences in the makeup of these two HCV patient subgroups.
The HERACLIS cohort, is the largest national HCV registry of patients treated with DAAs in tertiary liver centers from 2015 until 2024. Clinical data and characteristics were obtained from medical records, while transient elastography (TE) measurements and APRI score calculations were conducted at baseline. Patients were followed up initially for the duration of their treatment.

Results

930 patients were included in the study, 69.8% (n=649) of them were men with median age 52 years old and 9.2% of these had decompensated liver disease at DAA initiation. 56.8% (n=528) of this cohort were PWHD, while the rest had been infected in another manner (non-PWHD). When comparing these two populations, PWHD were younger in age (47.1±9,8 vs 56.9±13.1 years, p<0.001) and with lower BMI (24.4±4.4 vs 26.4±4.7 kg/m2, p<0.001). Non-PWHD cases had more often diabetes (13.6% vs 2.7%, p<0.001), hypertension (10.7% vs 8.8%, p<0.001) as well as decompensated liver disease (13.5% vs 6.1%, p<0.001). This was also reflected by TE measurements (13.9±10.9 vs 10.9±7.7 kPa, p=0.001) but not by the APRI score. Moreover, PWHD patients tended to have been more often infected with genotype 3 (64% vs 30%, p<0.001) while for other genotypes no such stark differences were observed. There was no significant variance observed regarding DAA regimen use but non-PWHD patients tended to suffer more often from adverse events secondary to DAA treatment (3.1% vs 0.7%, p=0.001).

Conclusion

The Greek PWHD and non-PWHD populations of HCV patients seem to exhibit different baseline characteristics which may be relevant to treatment selection and long-term follow up regimens. The main differences observed imply the concomitant presence of an element of metabolic syndrome in the non-PWHD cohort with a subsequent potential effect on the degree of underlying liver fibrosis.

Introduction

The surgical management of paraesophageal hernias (PEH) has evolved significantly, moving from open approaches including laparotomy or thoracotomy to minimally invasive techniques, including laparoscopic and robotic-assisted repair with or without fundoplication. Surgery aims to improve symptoms with better quality of life (QoL) and reduce the risk of life-threatening complications of PEH. Many reports are predominantly those with short or medium follow-up periods.

Aims & Methods

The present study aims to assess a large cohort of patients who had surgery for PEH for recurrence and QoL over a longer period. So, we did a retrospective analysis of prospectively collected data of patients who underwent surgery for symptomatic PEH from January 2001 to September 2024. Data collected on clinical presentation, surgical management, post-operative clinical outcomes, and follow data that comprised of clinical evaluation with basic, functional and radiographic assessment as well as quality-of-life (QoL) assessment of general health, physical, emotional, and social components with SF-36 questionnaire.

Results

There were 284 patients (180 females) with median age of 67 years (See Table) who underwent surgery for PEH. One hundred and sixteen presented with shortness of breath (41%). One hundred and twenty-seven (45%) were ASA III, 167 (59%) had microcytic anaemia.
Seven (2.5%) underwent gastropexy only. A fundoplication was performed in 146 (51%) during PEHR. The remaining 131 patients had PEHR plus gastropexy, with 30 of them were for recurrence following previous PEHR (16 of them had primary surgery elsewhere with fundoplication at PEHR)
Approach was robotic (35), laparoscopic (224), converted- to-open (7) or open (19). Median hospital stay was significantly lower in robotic 3 days (2-7) and laparoscopic group; 4 days (1-16) compared to open of 10 days (5-33). Mortality was 0.7% (2/284).
Median follow-up was 12 years. Symptoms improved in 232 (82%) with a significant improvement of respiratory function following PHER. Haemoglobin levels improved from 96g/L (61-123) preoperatively to 129g/L (98-138) postoperatively so was all components of QoL. Sixty-two (22%) had radiological recurrences but only 14 (5%) had clinical recurrence requiring further surgery and 11 (79%) of 14 were those who had a fundoplication at previous PEHR.

Conclusion

Para-oesophageal hernia repair is safe with good outcomes in all age groups with improvement in symptoms, quality of life, respiratory function, and associated anaemia. Radiological recurrences are not uncommon on long-term follow-up and does not need any intervention unless symptomatic. Para-oesophageal hernia repair combined with gastropexy avoiding fundoplication probably reduce symptomatic recurrences.

References

Lazar DJ, Birkett DH, Brams DM, Ford HA, Williamson C, Nepomnayshy D. Long-Term Patient-Reported Outcomes of Paraesophageal Hernia Repair. JSLS. 2017 Oct-Dec;21(4):e2017.00052. doi: 10.4293/JSLS.2017.00052. PMID: 29162971; PMCID: PMC5683814.

Introduction

The intestinal epithelium maintains host-microbiota homeostasis, with inflammation-associated pathological shifts in intestinal epithelial cell (IEC) subtypes. RNA N6-methyladenosine (m6A) modifications have been implicated in intestinal homeostasis; however, the underlying mechanisms remain poorly understood。

Aims & Methods

This study investigates the role of m6A methyltransferase METTL3 in regulating IEC subtype dynamics and epithelial-immune crosstalk during intestinal inflammation.
Tamoxifen was administered to the transgenic mice (Mettl3^flox/floxCdx2-Cre^ERT2) to induce intestine-specific Mettl3 knockout. Dextran sodium sulfate (DSS)-induced colitis was established, with body weight, disease activity index (DAI), and colon length monitored. Single-cell RNA sequencing (scRNA-seq) of colonic epithelium, combined with m6A-seq and RNA-seq, identified METTL3-dependent epitranscriptomic and transcriptional networks. Mouse colon organoids were used for functional validation.

Results

METTL3 is enriched in intestinal stem cells and transit-amplifying cells (TACs) and upregulated in human/murine inflammatory bowel disease. Mettl3 knockout mice exhibited exacerbated DSS colitis, marked by severe weight loss, elevated DAI, and colon shortening. scRNA-seq revealed METTL3 ablation depleted epithelial lineages (TACs, goblet cells, enterocytes) while amplifying immune infiltration (macrophages, neutrophils, T cells). METTL3 loss compromised the multipotency of TACs, particularly causing a blockade in goblet cell lineage commitment. Furthermore, it boosted TNF expression and amplified the signaling from IECs to neutrophils. Mechanistically, METTL3 induced m6A modifications on Slc39a8 mRNA, thereby regulating its expression. Slc39a8 knockdown in mouse colon organoids recapitulated METTL3 deficiency in impairing self-renewal.

Conclusion

Our work establishes METTL3 as a dual guardian of intestinal homeostasis, preserving epithelial regeneration and calibrating epithelial-immune dialogue by regulating Slc39a8 expression through m6A modification.