Introduction

Corpus atrophic gastritis(CAG) is a disease characterized by impaired gastric acid secretion and hypochlorhydria with increased risk of gastric cancer, especially in patients with Helicobacter pylori(Hp) infection. Efficacy of eradication therapy regimens(ETR) are commonly reported in association with pump pomp inhibitors(PPIs). In CAG patients, PPIs are not indicated. The efficacy of ETR without PPIs may be different from that with PPIs. Data on the efficacy and safety of ETR without use of PPIs in the CAG patients are lacking.

Aims & Methods

This study aimed to assess the eradication rate(ER) and safety of modified ETR with single-pill bismuth-based therapy without PPIs(SPBTnoPPIs) compared to (i) other ETR, amoxicillin-based therapy, without PPIs(ABTnoPPIs) in CAG patients, and (ii) ETR with SPBT therapy with PPIs(SPBTandPPIs) in no-CAG patients, in the first-line treatment of Hp infection.
In this retrospective study, a total of 113 consecutive patients histologically Hp positive were included between 2001 and 2020: CAG was diagnosed in 76 patients [77.6% females, median age 58.5 years(26-88)], and 37 patients were not affected by CAG [51.4% females, median age 58(22-81)].
CAG patients received SPBTnoPPIs: a modified ETR with SPBT(containing bismuth, tetracycline, metronidazole) without PPIs for 13 days, 3 pills t.i.d. since 2015(when placed on the market), or ABTnoPPIs: a sequential or concomitant amoxicillin-based therapy with or without bismuth, without PPIs before 2015. No-CAG patients received SPBTandPPIs: SPBT for 13 days, 3 pills t.i.d., with single dose of PPI in the morning, 30 min before breakfast.
The efficacy of Hp treatment was assessed by histopathology in all patients at 6 ± 3 months after treatment. Biopsy protocol and histopathological evaluation were performed according to the updated Sydney system. ER was expressed according to intention-to-treat(ITT) and per-protocol(PP) approach.

Results

46 and 30 CAG patients underwent SPBTnoPPIs and ABTnoPPIs, respectively. 3(6.5%) patients on SPBTnoPPIs and 2(6.7%) patients on ABTnoPPIs did not complete therapy(by patient’s decision)(p=1.00).
The 37 no-CAG patients were treated with SPBTandPPIs. No patients in this group interrupted the therapy.
In CAG patients, the overall ER at ITT and PP-analysis was 88.2% and 90.1%, respectively. In no-CAG patients, the overall ER was 80.4%(both at ITT and PP-analysis).
CAG-patients treated with SPBTnoPPIs compared to ABTnoPPIs showed a significantly higher ER at ITT-analysis(p=0.02) and at PP-analysis(p=0.01). CAG-patients treated with SPBTnoPPIs compared to no-CAG patients received SPBTandPPIs showed a higher ER at ITT-analysis(p=0.07), and a significantly higher ER at PP-analysis(p=0.02)(Table1).
4 CAG-patients(8.7%) patients on SPBTnoPPIs reported mild adverse events(1 abdominal discomfort, 1 nausea, 1 vomit, 1 diarrhea) compared to 2(6.7%) CAG-patients on ABTnoPPIs(1 abdominal discomfort, 1 vomit)(p=1.00). No-CAG patients did not report any adverse events(p=0.125).

Conclusion

A modified SPBT regimen without PPIs(3 days more but less pills/day) showed a high ER of about 95% in CAG patients with good compliance and tolerability.
This theraputical regimen may be considered beneficial in patients with CAG and it may be considered as first-line therapy in this specific setting.

Introduction

Autoimmune pancreatitis (AIP) is a rare disease that can be diagnosed, according to the International Consensus Diagnostic Criteria (ICDC). Contrast-enhanced MRI with MRCP has now largely replaced other imaging techniques and ERCP for the assessment of ductal morphology in AIP. A number of MRI-criteria have been proposed, but due to the rarity of the disease the diagnostic imaging criteria have not yet been systematically validated. Aim of the study is to review and optimize the MR-morphologic diagnostic criteria for AIP in terms of specificity and sensitivity in the diagnosis and differential diagnosis of the pancreaticobiliary system.

Aims & Methods

We analyzed retrospectively hundred-fiftysix (n=156) high-quality MRIs: AIP n=56, chronic pancreatitis (CP) n=25, pancreatic cancer (PDAC) n=25, primary sclerosing cholangitis (PSC) n=25, Non-HPB subjects n=25. The MRI reading was conducted in a blinded fashion, using defined criteria by at least two radiological experts. The statistical analysis was performed by means of Proportion test, Chi-square test or Fisher’s exact test, One-way ANOVA and Cohen’s Kappa Statistic of the level of agreement.

Results

The level of agreement between two readers was moderate to substantial agreement (κ 0.23-0.85). Sausage-like enlargment (Reader 1: Sens 30.91%, Spec 98.98%, NPV 71.85%, accuracy 74.51%; Reader 2: Sens 26.79%, Spec 98.00%, NPV 70.50%, accuracy 72.43%), restricted diffusion (Reader 1: Sens 47.83%, Spec 89.29%, NPV 75.76%, accuracy 74.51%; Reader 2: Sens 56.86%, Spec 73.26%, NPV 74.12%, accuracy 72.30%), delayed enhancement in the venous phase (Reader 1: Sens 8.70%, Spec 83.15%, NPV 63.79%, accuracy 74.10%; Reader 2: Sens 32.61%, Spec 79.31%, NPV 69.00%, accuracy 75.19%), the icicle sign (Reader 1: Sens 10.91%, Spec 100%, NPV 66.67%, accuracy 65.30%; Reader 2: Sens 37.50%, Spec 91.00%, NPV 72.22%, accuracy 71.79%) and hyperenhancement of ductal wall (Reader 1: Sens 14.29%, Spec 96.67%, NPV 67.44%, accuracy 71.90%; Reader 2: Sens 8.51%, Spec 95.45%, NPV 66.14%, accuracy 74.10%) show a good accuracy distinguishing AIP from controls. Apparent diffusion coefficient (ADC) was significantly different between AIP, PDAC and CP (ANOVA). The area under the receiver operating characteristic curve (AUROC) was 0.85 (CI 0.73 – 0.97) and 0.68 (CI 0.51 – 0.85) respectively for CP and PDAC.

Conclusion

Our study showed that the Sausage-like enlargment, restricted diffusion, delayed enhancement in the venous phase, the icicle sign and hyperenhancement of ductal wall show a good accuracy distinguishing AIP from controls.

Introduction

Infection with SARS-CoV-2 leads to pronounced changes in the intestinal microbiome and also decay of tryptophan that are both related to disease severity. Supplementation of tryptophan metabolism using ileocolonic-release nicotinamide may stabilize the microbiome and alleviate COVID-19 symptoms.

Aims & Methods

This prospective, double-blind, randomized, placebo-controlled trial evaluated safety and efficacy of a 4-week intervention with a novel oral formulation of nicotinamide (1,000 mg/d) in symptomatic, unvaccinated, non-hospitalized outpatients with PCR-proven early COVID-19. The primary outcome was full recovery from reduced physical performance after 2 weeks in the prespecified symptomatic primary analysis population with at least one risk factor for severe COVID-19. Stools from a part of the patients (4 timepoints) were submitted to 16S rRNA (n=70) and shotgun metagenomics (n=18) sequencing.

Results

Screening of 7,013 patients resulted in randomization of 900 participants (nicotinamide or placebo (1:1), from which 867 received the investigational product and 500 qualified for the acute disease analysis population. 110 of 191 patients (57.6%) receiving nicotinamide and 80 of 188 patients receiving placebo (42.6%) recovered from their performance drop at week 2 (absolute difference, 15.0 percentage points; odds ratio, 1.33; 95% confidence interval, 1.03 to 1.70; P=0.004). Nicotinamide was also superior in the secondary endpoints ability to perform normal activities (P=0.009) and shortness of breath (P=0.012). Substantial effects on gut microbiome constitution were seen counteracting COVID-19 related changes. Reduction of tryptophan biosynthesis in the microbiome in placebo patients was restored and NAD salvage pathways were activated in nicotinamide-treated individuals. No relevant safety signals were observed.

Conclusion

Oral treatment with nicotinamide stabilized the gut microbiome against COVID-19 related changes and led to faster recovery of physical performance in symptomatic patients at risk for severe Covid-19. (Funded by the German Research Foundation [DFG], the State of Schleswig-Holstein and the UEG Research Prize; ClinicalTrials.gov number: NCT04751604)

Disclosure

SS reports indirect stock ownership in Gerion Biotech GmbH as well as consulting and personal fees from AbbVie, Allergosan, Amgen, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Galapagos/Gilead, HIKMA, I-Mab, Janssen, Lilly, Morphic, MSD, Mylan, Pfizer, Prometheus, Protagonist, Provention Bio, Sandoz/Hexal, Takeda, and Theravance.
GHW is employed part-time by CONARIS Research Institute AG (Kiel, Germany).
TB reports consulting fees, honoraria or other support from AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Merck, MSD, Novartis, Pfizer, and Roche.
KA reports consulting fees, honoraria or other support from AbbVie, Falk, Galapagos, Janssen, Pfizer, and Takeda.
ML reports a lecture honorarium and travel support by AstraZeneca.
PR reports stock ownership in Gerion Biotech GmbH and consulting fees from Takeda.

Introduction

While understanding the cause is pivotal for managing acute pancreatitis (AP), there is currently no established protocol for determining its aetiology. Ongoing research aims to validate diagnostic protocols and integrate advanced tests for cases of idiopathic acute pancreatitis (IAP). This study evaluated current international opinion about diagnosis and follow-up of IAP.

Aims & Methods

An international survey was conducted through an online survey platform; the link was shared through social media, e-mails and conference presentations. Responses were collected anonymously. The 37 questions were developed by an international multidisciplinary team, part of a Pancreas2000 collaborative project.

Results

Respondents (n=247) were from over 35 countries; 39% of them had over 10 years of clinical experience; 73% were working in tertiary referral centres; 56% were gastroenterologists, 34% surgeons. An equal number of respondents (n=85, 34%) chose magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) as the first test ideally performed in case of no suspected aetiology for AP after basic tests. When both investigations were available in the respondents’ centre, 44% chose other tests, 30% MRCP and 27% EUS. If there is no evidence of biliary aetiology, 79% of respondents would not perform cholecystectomy; the rest would choose recurrent AP and a history of elevated liver enzymes as main indications. No correlation was found when comparing tertiary and non-tertiary centres in performing cholecystectomies, similarly when comparing centres with or without EUS availability. Most respondents (90%) followed up on moderate and severe AP cases without an aetiology at index admission; 53% of centres followed up on all the IAP cases after first discharge. The follow-up was mostly done by gastroenterologists (62%); 33% of specialists would conduct a follow-up visit every 6 months, while 17% wouldn’t recommend follow-up visits.

Conclusion

This international survey highlights the lack of standardisation for diagnosis and follow-up of IAP. Although MRCP and EUS were ideally chosen as first options in IAP diagnosis, respondents chose other investigations in their practice even when both were available. Only half of the centres schedule visits, showing a lack of consensus regarding follow-up. There is a need for international standardisation for diagnosis and follow-up of IAP.

Introduction

Computer Aided Detection (CADe) systems may improve detection of (pre-)malignant lesions by endoscopists. Most CADe systems are developed using homogeneous datasets collected by experts, which do not represent the heterogeneous imaging conditions of daily clinical practice. Such heterogeneity is caused by endoscopist-dependent variation (e.g. skill and experience) as well as endoscopist-independent variation (e.g. endoscopy equipment). Recently, we presented a CADe system for Barrett’s neoplasia¹. However, all training and test data originated from expert centers.

Aims & Methods

We aimed to develop an updated CADe system (CADe 2.0) demonstrating more robustness to the varied imaging conditions found in routine patient care.
Our previously published CADe system (CADe 1.0) was trained and internally validated on a high-quality dataset originating from 15 expert centers. The dataset included 6.337 neoplastic (1.362 patients) and 7.695 non-dysplastic images (1.139 patients).
The updated CADe system (CADe 2.0) underwent four improvements. First, we included more heterogeneous training data from our training set patient population. We extracted video frames from videos comprising various quality artefacts (e.g. blurred lenses or insufficient mucosal cleaning). Second, we applied advanced data augmentation methods to address the diversity of post-processing enhancement settings used by modern endoscopy systems. Third, we updated the CADe system with a Vision Transformer architecture², which has shown to improve performance on lower quality endoscopic images³. Finally, we transitioned our pretraining approach from semi-supervised to a self-supervised learning framework⁴.
Both CADe systems were evaluated using three prospectively collected, independent test sets. The first test set represented the true diversity and complexity encountered in daily clinical practice. This dataset comprised all videos captured from all included patients in five referral centers between April 2022 and January 2024 (431 ten-second BE videos from 115 patients). The second test set focused on endoscopist-dependent variation. It included three paired subsets with high, moderate and low-quality images from 122 patients. Quality was determined by factors such as esophageal expansion and mucosal cleaning. The third test set addressed endoscopist-independent variation. It contained 16 paired subsets of 396 images (122 patients). Every subset was based on a different post-processing enhancement setting of the endoscopy system.

Results

For test set 1, CADe 1.0 reached a sensitivity and specificity of 84% and 73%. CADe 2.0 scored 93% and 76%. For test set 2, CADe 2.0 reached higher sensitivity and specificity scores on high-quality images compared to CADe 1.0. In addition, CADe 2.0 performance loss on moderate and low-quality images was smaller. On test set 3 CADe 1.0 scores substantially varied depending on the test sets enhancement setting (82-94% sensitivity, 52-83% specificity). Variation of CADe 2.0 was limited to 91-95% and 81-88%.

Table 1. Results of CADe 1.0 and CADe 2.0

Conclusion

The updated CADe system displayed improved performance for detection of Barrett’s neoplasia in videos. More importantly, this CADe system also displayed less performance loss when exposed to lower image quality and less performance variability when confronted with differing post-processing enhancement settings.

References

1. Fockens N, Jong MR, Jukema JB, Pouw RE, Duits LC, Van Munster SN, et al. A deep learning system for detection of early Barrett's neoplasia: a model development and validation study. The Lancet Digit Health. 2023;5:905-21.
2. Yu W, Si C, Zhou P, Luo M, Zhou Y, Feng J, et al. MetaFormer Baselines for Vision2022 October 01, 2022:[arXiv:2210.13452 p.]. Available from: https://ui.adsabs.harvard.edu/abs/2022arXiv221013452Y.
3. Kusters CHJ, Boers TGW, Jaspers TJM, Jukema JB, Jong MR, Fockens KN, et al., editors. CNNs vs. Transformers: Performance and Robustness in Endoscopic Image Analysis. Applications of Medical Artificial Intelligence; 2024 2024//; Cham: Springer Nature Switzerland.
4. Caron M, Touvron H, Misra I, Jégou H, Mairal J, Bojanowski P, et al. Emerging Properties in Self-Supervised Vision Transformers2021 April 01, 2021:[arXiv:2104.14294 p.]. Available from: https://ui.adsabs.harvard.edu/abs/2021arXiv210414294C.

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is a cornerstone in the diagnosis and treatment of pancreatobiliary diseases. However, it carries the risk of complications including potentially fatal post-ERCP pancreatitis (PEP). Despite ongoing efforts, effective strategies for managing PEP remain unestablished. Current guidelines define PEP based on symptoms and findings occurring within 24 hours after ERCP; however, early diagnosis and intervention may prevent its incidence and severity. Recently, urinary trypsinogen-2 (UT2) has emerged as a potential biomarker for early acute pancreatitis, but its role and the optimal timing for PEP remain unclear. Therefore, we aimed to evaluate the diagnostic performance of UT2 at multiple time points following ERCP.

Aims & Methods

This is a single-center prospective observational study conducted at The University of Tokyo Hospital. Patients who underwent their initial ERCP at our institution between February 2022 and June 2024 were enrolled. Patients with choledochojejunostomy, biliary pancreatitis, or those undergoing hemodialysis were excluded. UT2 levels were measured using a rapid dipstick test before ERCP, immediately after, and at 1 and 3 hours post-procedure. Serum amylase (AMY) levels were measured 3 hours after ERCP. We evaluated the diagnostic performance (sensitivity, specificity, and accuracy) of UT2 at multiple time points, for the diagnosis of PEP. PEP was defined as an elevation in pancreatic enzyme >3x upper limit of normal with abdominal pain at 24 hours post-pocedure.

Results

A total of 521 patients underwent initial ERCP during the study period, and 337 were included in the final analysis. The median age was 74 years, and 64% were male. A naïve papilla was present in 89% of patients. The indications for ERCP included bile duct stones (39%), malignant biliary obstruction due to pancreatic cancer (13%) or non-pancreatic cancer (18%), benign biliary stricture (5%), diagnostic pancreatogram (24%), and others (1.2%). EST, EPBD, and EPLBD were performed in 37%, 6.5%, and 4.5%, respectively. Prophylactic pancreatic stent placement and rectal NSAIDs administration were performed in 29% and 20%, respectively. PEP occurred in 10% (mild 8.6%, moderate 1.2%, and severe 0.3%) of patients. UT2 demonstrated a trend toward higher sensitivity compared to AMY (AMY: 52.9% vs. UT2 at 0 h: 52.9%, 1 h: 64.7%, 3 h: 64.7%), while AMY exhibited significantly higher specificity (AMY: 92.7% vs. UT2 at 0 h: 65.3%, 1 h: 64.7%, 3 h: 65.0%) and accuracy (AMY: 88.7% vs. UT2 at 0 h: 64.1%, 1 h: 64.7%, 3 h: 65.0%). Notably, 28.5% of patients were positive for UT2 prior to undergoing ERCP. These patients were significantly older (79 vs. 71 years, P < 0.01), more likely to have pancreatic cancer (19.8% vs. 9.5%, P = 0.02), and less likely to have chronic pancreatitis (3.1% vs. 12.9%, P = 0.01). After excluding 96 cases (28.5%) who were UT2-positive before ERCP, we further evaluated the diagnostic performance of UT2 and AMY. UT2 at 0 h had lower sensitivity compared to AMY (AMY: 54.2% vs. UT2 at 0 h: 37.5%, 1 h: 54.2%, 3 h: 54.2%). In contrast, specificity was similarly high across all markers (AMY: 91.7% vs. UT2 at 0 h: 88.9%, 1 h: 87.1%, 3 h: 87.1%). Diagnostic accuracy was comparable between AMY and UT2 (AMY: 88.0% vs. UT2 at 0 h: 83.8%, 1 h: 83.8%, 3 h: 83.8%).

Conclusion

UT2 showed slightly lower predictive performance for PEP compared to AMY. However, excluding UT2-positive pre-ERCP improved the diagnostic accuracy. The diagnostic performance plateaued at 1 hour after ERCP, suggesting its potential utility in predicting PEP earlier.

Disclosure

The author is affiliated with Nipro Corporation through a labor-related arrangement, but has received no financial support or remuneration related to this study.

Introduction

Cholangiocarcinoma (CCA) prevalence is high in East and Southeast Asia, especially in northeast Thailand. The first line of treatment for unresectable CCA is systemic chemotherapy which a median OS of less than 1 year under palliative systemic therapy. Albumin-Bilirubin (ALBI) prognosis score is the new method for the evaluation of liver performance status and prediction of treatment outcome but there is a lack of data in CCA patients.

Aims & Methods

Aim: To study the association of overall survival and ALBI prognostic score in unresectable CCA patients who received systemic chemotherapy.
Methods: This retrospective cohort study was conducted in Maha Chakri Sirindhorn Medical Center, Thailand. Demographic data, Clinical information, Laboratory profile, and survival analysis were extensively reviewed in the patient who received systemic chemotherapy from 2012 - 2022. All patients were monitored for at least 1 year after initial treatment with chemotherapy or until death.

Results

​69 patients of Unresectable CCA received systemic chemotherapy enrolled in this study. Most of the patients were men (45/69, 65.22%) and Intrahepatic type CCA (55/69, 79.71%). 17 patients (24.6%) need Biliary drainage before systemic chemotherapy which median pre-drainage TB was 11.35 mg/dL (10.7 – 20.6). Most ALBI prognostic score were group 2 (37/69, 53.6%) and anemia was significantly in ALBI 2 group (81.08%, P <0.001). The median overall survival was 10.23 months and the median progression-free survival was 5.77 months. Significantly better overall survival of the ALBI 1 group compared with the ALBI 2 group (ALBI 1, 13.76 months; ALBI 2, 6.33 months; log-rank test, P <0.001). The estimated 6, 12, 18, and 24-month survival rates were 72.46%, 40.58%, 18.84%, and 8.70%, respectively, whereas the estimated progression-free survival rate at 6, 12, 18, and 24 months were 47.83% and 10.14%, respectively.

Conclusion

ALBI prognosis score may serve as a surrogate marker in predicting the overall survival and progression-free survival of CCA patients who received Systemic chemotherapy.

References

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Disclosure

There is no any conflict of interest in this study