Clinical Case Summary

Our patient was a 66yr Chinese man who was treated for active Chronic Hepatitis B from 2009 with Lamivudine, Adefovir and then switched to Tenofovir from 2020 with long term undetectable Hepatitis B viral load (HBV VL) and normal Liver function tests. His ultrasound liver was normal and Fibroscan 6.9kpa in 2021. Hepatitis B Surface quantification was 87 IU/ml. ALT 28.
The patient was enrolled in a research trial which randomized him to stopping Tenofovir with close follow up.
At week 4 after stopping Tenofovir, his HBV VL became detectable at 2.53log and ALT 31.
At week 8, his HBV VL increased to 5.55log and ALT 35.
At week 10, HBV VL was 6.85, ALT 384, Bilirubin and INR normal. HBeAg remained negative and the patient remained asymptomatic.
He was promptly restarted on Tenofovir but his ALT continued to rise and peaked at 832 at week 12 before gradually returning to normal as did his Hepatitis B viral load.
At week 13, he developed tingling over his hands and feet.
At week 14, he was admitted for clumsiness with reduced sensation over the feet and hands. He had no other systemic symptoms suggestive of any infections.
Examination revealed subjective reduction in sensation over the distal peripheral limbs. Power was normal but reflexes were absent over the ankles and knees.
MRI brain was normal.
Lumbar puncture showed high CSF protein 0.7gL but normal cell count. Nerve Conduction study (NCS) reported acute inflammatory demyelinating polyneuropathy.
EMG was unremarkable.
A probable diagnosis of GBS was made.
His ALT was down to 304 and HBV VL 3.82 log.
NCS repeated 2 months later and showed similar inflammatory demyelinating polyneuropathy.
NCS repeated 4 months later showed significant improvement which confirmed a diagnosis of GBS
1 year from his first presentation, he recovered fully.
Only 7 cases of Hepatitis B related GBS have been reported in the literature. Our case highlights GBS resulting from Hepatitis B flare

References

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Introduction

Prophylactic total gastrectomy (PTG) is the definitive treatment for hereditary diffuse gastric cancer syndrome (HDGC). Endoscopic surveillance informs the requirement and optimal timing to surgery. However, endoscopic recognition of early signet ring cell carcinoma (SRCC) remains challenging. In this study, we aimed to develop and prospectively validate a user-friendly diagnostic framework with machine-learning to support endoscopists in accurate identification of early SRCC during surveillance in HDGC individuals.

Aims & Methods

We retrospectively analysed 147 HDGC individuals undergoing endoscopic surveillance to evaluate the diagnostic accuracy of endoscopic criteria (Cambridge criteria), develop a clinical decision tree (cDT) to better apply the criteria based on machine leaning, and investigate its clinical significance. We then prospectively validated cDT in 66 CDH1 pathogenic-variant carriers. The inter-observer agreement and diagnostic accuracy of Cambridge criteria and cDT were assessed through multi-reader multi-case study.

Results

Retrospective analysis of 537 endoscopies showed Cambridge criteria achieved 82.8% (48/58) sensitivity and 78.2% (140/179) specificity for SRCC diagnosis. The presence and number of neoplastic pale areas are independent predictors of higher cancer burden in HDGC individuals. In prospective study, cDT had 77.8% (21/27) sensitivity and 90.7% (49/54) specificity. The cDT significantly improved average sensitivity among non-experts from 66.7% to 72.5% and 87.5%, and among experts from 74.1% to 80.0% and 91.7% (P = 0.03).

Conclusion

We developed and validated a practical endoscopic framework to enhance SRCC assessment during HDGC endoscopic surveillance.

Introduction

Hereditary diffuse gastric cancer (HDGC) associated with CDH1 germline pathogenic variants (PV), carries a high lifetime risk of signet ring cell carcinoma (SRCC). Clinical and molecular events driving progression from early SRCC to advanced cancer are elusive, therefore there is uncertainty to whom and when to recommend risk reducing total gastrectomy (RRTG). We hypothesise a high number of early SRCC lesions (SRCC burden) could be a risk factor for progression to clinical gastric cancer. This study aimed to identify predictors of SRCC burden and provide evidence to modify surveillance intervals.

Aims & Methods

We analyzed data from 53 CDH1 PV carriers who underwent RRTG prospectively recruited between Jan 2006 and Dec 2024 (RRTG dataset) and a separate cohort of 95 CDH1 carriers with ≥2 surveillance endoscopies and 0-2 positive biopsies at baseline (endoscopy dataset). Targeted biopsies (TB) and systematic random biopsies (RB) were obtained using the Cambridge protocol. Multivariable negative binomial regression was used to assess the association of clinical (age, sex, family history, ethnicity, CDH1 variant type) and endoscopic factors (mean number of positive TB and RB per endoscopy) with SRCC burden in RRTG specimens. A logistic regression model with significant predictors was trained to classify patients into low (≤20 foci) and high (>30 foci) cancer burden, validated over 1,000 iterations. Temporal trends in biopsy findings were analyzed using linear mixed-effects models in endoscopy dataset. Surveillance effectiveness at 6- and 12-month intervals was compared in a subset of 38 patients with at least one positive endoscopy followed by subsequent surveillance.

Results

Among 53 RRTG patients (median: 3 surveillance endoscopies over 19 months), 47 (90%) had pT1aN0M0 cancer, and 6 (11%) had pT0N0M0. The mean number of SRCC foci on RRTG specimens was 13, with a median of 33 (IQR: 2-37) and a range of 0 to 273. Among clinical factors, whereas the average number of positive TB (p = 0.001) and RB (p < 0.001) per endoscopy were independent predictors. The model based on endoscopy factors achieved an AUC of 0.88 (0.87, 0.89) for predicting cancer burden under RRTG. No significant trend in biopsy positivity over time was observed (Estimate = 0.0046, p = 0.176). Extending surveillance intervals from 6 to 12 months in patients with low-level positivity did not significantly reduce detection of increased positive biopsies (22% vs. 19%, p = 0.78). Furthermore, using ≥3 positive biopsies as a trigger for recommending RRTG, only 6 patients (16%) met this threshold. The median time after the first positive endoscopy to meeting this criterion was 9 months (95% CI: 0-29) under the 6-month surveillance strategy and 12 (95% CI: 3-33) months under the 12-month surveillance strategies.

Conclusion

Endoscopic surveillance using targeted and random biopsies by experienced endoscopists provides a reliable estimate of SRCC burden in HDGC. Our findings suggest that extending surveillance intervals and delaying surgery in patients with low early SRCC burden is clinically safe.

Introduction

While the link between oral hygiene and systemic disease has been widely studied, large-scale studies specifically examining the association between oral hygiene or periodontal disease (PD) and colorectal cancer (CRC) remain scarce.

Aims & Methods

We aimed to investigate the association between oral hygiene indicators and the risk of CRC using a nationwide, population-based dataset from the Korean National Health Insurance Service (NHIS). The first was based on the National Health Screening (NHS) database, incorporating self-reported oral hygiene behaviors and dentist-conducted clinical dental examination findings. The second analysis utilized claims data from the NHIS database, focusing on PD as the primary exposure. We identified individuals aged ≥19 years newly diagnosed with CRC between January 2012 and December 2019, and controls without any history of cancer, matched at a 1:4 ratio using extensive propensity score (PS) matching. Multivariable conditional logistic regression was performed to adjust for potential confounders, including demographics, comorbidities, lifestyle factors, and laboratory values.

Results

In the NHS-based analysis, a total of 2,188,968 individuals were analyzed. Following PS matching, the matched dataset comprised 35,668 CRC cases and 141,850 controls. Several oral health indicators were significantly associated with increased CRC risk, including objective dental findings such as decayed teeth (adjusted odds ratio [aOR], 1.08; 95% confidence interval [CI], 1.05–1.11), missing teeth (aOR, 1.14; 95% CI, 1.11–1.17), severe gingivitis (aOR, 1.21; 95% CI, 1.15–1.26), and dental calculus (aOR, 1.10; 95% CI, 1.07–1.12), as well as poor oral hygiene-related behaviors or symptoms such as infrequent dental visits (aOR, 1.04; 95% CI, 1.02–1.07), poor perceived oral health (aOR,1.06; 95% CI, 1.02-1.10),
infrequent daily toothbrushing (aOR,1.20; 95% CI, 1.14–1.24), infrequent brushing before bedtime (aOR, 1.05; 95% CI, 1.02–1.08), non-use of interdental cleaning devices (aOR, 1.10; 95% CI, 1.07–1.13), and tooth pain (aOR, 1.03; 95% CI, 1.00–1.06). In the claims-based analysis, among 5,266,776 individuals, 133,482 CRC cases and 528,559 matched controls were included after PS matching. In the multivariable analysis, PD was independently associated with an increased risk of CRC (aOR, 1.03; 95% CI, 1.01–1.04). Additionally, in subgroup analyses stratified by age, sex, alcohol consumption, smoking status, and obesity, objective dental examination findings consistently showed a significant association with increased CRC risk across all subgroups.

Conclusion

Poor oral hygiene and PD were significantly associated with an elevated risk of CRC in this large-scale, population-based study. These findings highlight the potential importance of oral health in screening and prevention of CRC.

Introduction

Endoscopic resection techniques, such as Endoscopic Mucosal Resection (EMR) and Endoscopic Submucosal Dissection (ESD), are used to remove precancerous and early-stage cancerous lesions in the gastrointestinal tract. While ESD is the gold standard due to its en-bloc and R0 resection capability, Underwater Endoscopic Mucosal Resection (UEMR) has emerged as an alternative. UEMR uses water buoyancy to aid lesion resection, potentially improving safety and reducing procedure time. However, its comparative effectiveness remains unclear.

Aims & Methods

The primary aim of this systematic review and meta-analysis is to compare the efficacy, safety, and procedural efficiency of Underwater Endoscopic Mucosal Resection (UEMR) versus Endoscopic Submucosal Dissection (ESD) in the treatment of gastrointestinal lesions.
A systematic search was conducted in PubMed, Embase, Google Scholar, Scopus, and Cochrane Library. Eligible studies compared UEMR and ESD in gastrointestinal lesions, providing data on en-bloc resection, R0 resections, adverse events, and procedure time. Randomized controlled trials (RCTs), cohort studies, and comparative studies were included.
Two reviewers independently extracted data, resolving discrepancies by discussion. Study quality was assessed using the Cochrane Risk of Bias Tool. Random-effects models were used for pooled analyses, calculating odds ratios (OR) and mean differences with 95% confidence intervals (CI). Heterogeneity was evaluated via the I² statistic.

Results

The analysis included four studies (three RCTs and one cohort study), with a total of 651 patients. Regarding efficacy, UEMR showed significantly lower en-bloc resection rates compared to ESD (OR = 0.01, 95% CI [0.01–0.06], Z = 6.85, p < 0.00001), suggesting a reduced ability to achieve complete lesion removal in a single piece. Similarly, R0 resection rates were also lower in the UEMR group (OR = 0.16, 95% CI [0.09–0.22], Z = 9.09, p < 0.0001), although with high heterogeneity (I² = 83%), possibly reflecting variations in patient selection, operator expertise, and technical differences among studies. In terms of safety, no significant difference was observed in adverse event rates between UEMR and ESD (OR = 0.48, 95% CI [0.10–2.34], Z = 0.90, p = 0.37), indicating comparable safety profiles. However, UEMR demonstrated an advantage in procedural time, being 5.89 times faster than ESD (p < 0.0001). This suggests that while UEMR may offer time efficiency, it comes at the cost of lower en-bloc and R0 resection rates, raising questions about its suitability for lesions requiring complete and margin-free excision. Further studies are needed to clarify the impact of these differences on long-term patient outcomes and to determine the optimal indications for UEMR in clinical practice.

Conclusion

UEMR offers a quicker alternative to ESD but lacks its high resection quality, making ESD preferable for lesions requiring en-bloc or R0 resection. Gastroenterologists must weigh UEMR’s speed against ESD’s superior efficacy. Standardizing UEMR techniques may improve its resection quality and expand its role in clinical practice. Future research should optimize UEMR and address variability in resection outcomes.

References

1. Nett A, Binmoeller K. Underwater Endoscopic Mucosal Resection. Gastrointest Endosc Clin N Am. 2019 Oct;29(4):659-673. doi: 10.1016/j.giec.2019.05.004.
2. Ferlitsch M et al. Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024. Endoscopy. 2024;56(1):1-20. doi: 10.1055/a-2304-3219.
3. de Souza MHG, Ribeiro IB, de Moura DTH, et al. Underwater versus conventional endoscopic mucosal resection for colorectal lesions: a systematic review and meta-analysis of randomized clinical trials. Surg Endosc. 2023;37(5):3456-3465. doi: 10.1007/s00464-022-09456-7
4. Chandan S, Mohan BP, Khan SR, et al. Safety and efficacy of underwater versus conventional endoscopic mucosal resection for colorectal polyps: Systematic review and meta-analysis of RCTs. Gastrointest Endosc. 2023;97(6):1087-1095.e3. doi: 10.1016/j.gie.2023.01.012.
5. Inoue T, Nishida T, Maekawa A, et al. Underwater endoscopic mucosal resection versus endoscopic submucosal dissection for 20–30 mm colorectal polyps: a prospective randomized study. Endoscopy. 2022;54(5):456-464. doi: 10.1055/a-1500-1234.
6. Park SS, Lee IS, Lee SH, et al. Comparison of underwater endoscopic mucosal resection and endoscopic submucosal dissection of rectal neuroendocrine tumors (with videos). Gastrointest Endosc. 2021;93(3):637-646.e2. doi: 10.1016/j.gie.2020.08.030.
7. Takeuchi Y, Uedo N, Hotta K, et al. Underwater endoscopic mucosal resection for colorectal lesions: Can it be an “Underwater” revolution? World J Gastroenterol. 2020;26(20):2545-2553. doi: 10.3748/wjg.v26.i20.2545.

Introduction

Several Randomized Controlled Trials (RCTs) have evaluated the role of artificial intelligence (AI) Computer-Aided Detection (CADe) systems to enhance polyp detection. However, these studies have focused exclusively on locally deployed hardware-based AI systems, whereas cloud-based systems may improve the accessibility and upgrading of CADe technology. ‘CADDIE’ (Odin Vision, an Olympus company) is a cloud-based CADe system that receives the live endoscopy image stream via the hospital’s internet network, where the AI algorithm processes the images, and overlays real-time bounding boxes on the endoscopy screen to highlight suspected polyps.

Aims & Methods

This prospective RCT aimed to evaluate the efficacy and safety of the novel cloud-based CADe-system in improving polyp detection.

This international, multi-centre, parallel-group RCT was conducted across eight centres in four European countries. Participating endoscopists had a baseline of >1000 colonoscopy procedures and an adenoma detection rate (ADR) of ≥25%. Patients aged ≥40 years and at average risk for colorectal cancer undergoing screening or surveillance indications for colonoscopy were recruited. Patients were randomised in a 1:1 ratio to standard colonoscopy (SoC) or CADDIE-assisted (CADe-arm) colonoscopy. The co-primary endpoints were superiority in adenomas per colonoscopy (APC) as the efficacy endpoint, and non-inferiority for the Positive Percent Agreement (PPA), defined as the percentage of resections that are histologically confirmed adenomas, SSLs and large (>10mm) hyperplastic polyps of the proximal colon, as the safety endpoint.

Results

Overall, 22 endoscopists and 841 participants were included in the analysis. The CADe-arm significantly increased APC by 33% (0.62 vs 0.82, Ratio 1.33 [95%CI 1.06-1.67], p=0.01) and ADR (35.9% vs 43.2%, difference of 7.3% [95%CI 0.7%-13.9%], p=0.03) compared to the SoC-arm. The mean detection of sessile serrated lesions (SSLs) (0.03 vs 0.08, Ratio 3.30 [95%CI 1.41-7.57], p<0.01), large adenomas (0.04 vs 0.09; Ratio 1.93 [95%CI 1.03-3.62], p=0.04), and large polyps (0.05 vs 0.12; Ratio 2.36 [95%CI 1.33-4.17], p<0.01) also significantly improved. A higher proportion of large polyps (27.3% vs. 37.0%) and large adenomas (15.8% vs 24.2%) were non-polypoid ‘flat’ morphology in the CADe-arm compared to the SoC-arm. Other detection metrics, including neoplastic polyps per colonoscopy (0.66 vs 0.91; Ratio 1.39 [95%CI 1.12-1.73], p<0.01) and polyps per colonoscopy (1.06 vs 1.41 (Ratio 1.35 [95%CI 1.13-1.61], p<0.01), also significantly increased.

Non-inferiority in PPA was achieved (53.4% vs 53.9%; 0.5% (-5.0%,∞)), with no increase in unnecessary resections.

Conclusion

This trial demonstrates the safety and efficacy of a cloud-based CADe-system to increase endoscopists' polyp detection across multiple metrics, notably for large adenomas, large polyps, and SSLs.

Disclosure

AR, CS, LBL, RK have received medical consultancy fees from Odin Medical Ltd

Introduction

Clostridioides difficile infection (CDI) is the most common cause of nosocomial diarrhoea, and
during the last decades its incidence has significantly increased, not only in the hospital setting but
also in the community (1). CDI includes severe clinical pictures of disease. Fecal microbiota
transplantation (FMT) is an established treatment for recurrent CDI, but its role in severe clinical
pictures of CDI is still not well defined.

Aims & Methods

Our aim is to report efficacy and safety of FMT in a large cohort of patients with severe and severe-
complicated CDI. We included patients with severe CDI treated with FMT at our center from June
2013 to August 2024. Severe and severe-complicated CDI were defined according to international
guidelines. Data was collected on patient demographics, CDI characteristics, including disease
severity, risk factors and concomitant diseases. Enrolled patients were followed up at 12 weeks after
the last FMT. The primary outcome was the clinical resolution of CDI at 8 weeks after FMT, while
the secondary outcomes were the overall survival at 90 days and the safety of FMT. Donor stools
were screened following international guidelines. Prior to fecal infusion, all patients underwent a 3-
day antibiotic pre-treatment regimen with oral vancomycin or fidaxomicin, as well as bowel
cleansing. FMT procedures were carried out by colonoscopy using a single-donor solution of at
least 50 grams of fresh or frozen feces. A sequential FMT approach was planned in patients with
pseudomembranous colitis (PMC), until the disappearance of pseudomembranes, or in patients who
experienced diarrhea after the initial FMT with a persistence of C. difficile toxin on stool samples.

Results

125 patients were enrolled (60.8% female, mean age 71 years). One-hundred and ten patients had
severe CDI (88%), 15 had severe complicated CDI (12%). Of them, 73 patients had
pseudomembranous colitis (58.4%). The median number of CDI recurrences was 2. A sequential
FMT protocol was performed in 62 patients (49.6%), for a total of 235 FMT procedures. Regarding
risk factors, the most frequent were hospitalization (107 patients – 85.6%), antibiotic use in the 30
days prior to infection (94 patients – 75.2%), chronic therapy with proton pump inhibitors (74
patients – 59.2%) and enticement (39 patients – 31.2%). The median Charlson Comorbidity Index
(CCI) was 5. Overall, 108 patients (86.4%) experienced resolution of CDI (97 with severe CDI and
11 with severe-complicated CDI). 18 patients (14.4%) died within the follow-up period. No deaths
were attributable to FMT. Severe adverse events occurred in 11 (8.8%) patients and 6 were
potentially associated with FMT and/or failure to cure CDI.

Conclusion

In our cohort of patients, FMT was a highly effective and safe treatment for severe and severe-
complicated CDI.

References

1 - Liu C, Monaghan T, Yadegar A, Louie T, Kao D. Insights into the Evolving Epidemiology of
Clostridioides difficile Infection and Treatment: A Global Perspective. Antibiotics (Basel). 2023 Jul
1;12(7).