Introduction

There has been a resurgence in the use of bismuth-quadruple therapy (PPI, bismuth, tetracycline and metronidazole) in Europe with the commercialization of a three-in-one single-capsule formulation, but the experience with this regimen is still limited.

Aims & Methods

To evaluate the effectiveness and safety of the three-in-one single-capsule in the European Registry on Helicobacter pylori management (Hp-EuReg).
International, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H. pylori management by European gastroenterologists. All infected adult patients treated with 10-day single-capsule according to data sheet (3 capsules/6h) or alternative three times a day (4 capsules/8h) prescriptions were systematically registered at AEG-REDCap e-CRF until January 2023. Variables included: Patient’s demographics, previous eradication attempts, prescribed treatment, adverse events, and outcomes. Modified intention-to-treat (mITT) and per-protocol (PP) analyses were performed, and data were subject to quality review.

Results

Of the 59,689 patients in the Hp-EuReg, 8,302 (14%) received single-capsule bismuth-quadruple therapy. The majority of these patients were naïve (75%), with an average age of 52 years, 62% female and 14% with peptic ulcer. Overall, the single-capsule achieved a high eradication rate based on the mITT (91.5%) and PP (92%) analyses. Effectiveness (mITT) was higher when using the single-capsule as a first-line treatment (93%), but it had also high effectiveness as a rescue therapy, both in second-line (87%) or subsequent lines of therapy (3^rd-6^th lines: 86%) (Table 1). Compliance with treatment (>90% of drug intake) was reported in 93% of cases and was the factor most closely associated with the effectiveness of treatment. Adverse events (26%) were generally mild-to-moderate and transient; only 0.1% of patients reported a serious adverse event, leading to the discontinuation of treatment in 1.7% of patients.

Conclusion

The 10-day treatment with single-capsule bismuth-quadruple therapy achieves H. pylori eradication in approximately 90% of patients by mITT in real-world clinical practice, both as a first-line and rescue treatment, with a favourable safety profile.

Disclosure

Olga P. Nyssen received research funding from Mayoly and Allergan.
Javier P. Gisbert served as speaker, consultant, and advisory member for or received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen.

Introduction

Rectal adenocarcinomas (ADC) are associated with a higher rate of recurrence but also with greater surgical morbidity when compared to those of the colon. Local excision (LE) of early colorectal ADC that meet curability criteria (CC) is associated with excellent outcomes, and only surveillance is recommended. However, in the presence of non-curative LE criteria, salvage treatment should be performed. Although in most cases this includes surgery with lymphadenectomy, another possible approach is radio +/- chemotherapy (RT/CRT) followed by surveillance, in a “watch and wait” (WW)-like strategy, with surgery only in case of persistence or recurrence of injury.

Aims & Methods

This work aims to evaluate oncological outcomes in a cohort of patients after LE of early rectal ADC without CC, submitted to different clinical options (surveillance, RT/CRT followed by WW and surgery).
It is a retrospective study including patients evaluated at two tertiary hospital centers for pT1/pT2 rectal ADC who underwent LE (endoscopic or transanal resection - TAR) between 12/2011-12/2022.
ADC pT1, low grade, sm1, without lymphovascular or perineural invasions, without high grade budding and with free margins were considered CC.
Clinical options in patients without CC, their complications and outcomes were analyzed.

Results

64 patients were included in which the CC for LE were not met (5 for pT2; 3 for high grade; 8 for lymphovascular invasion; 54 for positive resection margins; 36 for sm>1, 28 (44%) patients failed >1CC). Of these, 49 were male patients, mean age 65.4 years (44-88), 14 with a family history of colorectal cancer and 12 with current or past smoking habits. ADCs: 12 excised by polypectomy, 20 by mucosectomy, 26 by submucosal or intramuscular dissection, 1 endoscopic transmural resection; 2 TAR and 3 endoscopic+TAR resections; 47 lesions excised in a single fragment; 29 in flat lesions, 31 in sessile polyps, 4 in pedunculated polyps.
In 24 patients, surgery was performed with lymphadenectomy (4 with definitive colostomy); in 16 patients, only surveillance was performed (8 due to comorbidities; 2 due to risk of Abdominoperineal Resection; 4 due to LE > 12 weeks/unidentified site; 2 due to refusal of surgery); 19 patients received CRT and 5 only RT, followed by surveillance. There were CRT complications in 4 patients (grade 2/3) and surgery complications (grade II/III) in 6.
Average follow-up: 35 months; 3 relapses were identified in the surveillance only group (19%) – 2 local and 1 distant; 1 distant recurrence in the surgery group (4%); 1 local and 1 local+distant recurrence in the RT/CRT group (8%). All recurrences occurred in pT1. Two of the patients with recurrence died of the disease (1 of them had undergone surveillance, the other had surgery with lymphadenectomy).

Conclusion

Despite the short series, this work confirms the worse outcome of patients with malignant polyps and pT2 of the rectum excised without CC and only monitored, and supports promising results from RT/CRT; this may be an organ-preserving option with less morbidity than surgery in patients with malignant rectal polyps excised without CC.

References

. Saraiva S, Rosa I, Fonseca R, Pereira AD. Colorectal malignant polyps: a modern approach. Ann Gastroenterol. 2022 Jan-Feb;35(1):17-27. doi: 10.20524/aog.2021.0681.
. Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, Arnold D. ESMO Guidelines Committee. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv22-iv40. doi: 10.1093/annonc/mdx224. Erratum in: Ann Oncol. 2018 Oct 1;29(Suppl 4):iv263.
. Al-Hawary M, Azad N, Chen Y, Ciombor K et al. Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022 Oct;20(10):1139-1167. doi: 10.6004/jnccn.2022.0051.
. Bernier L, Balyasnikova S, Tait D, Brown G. Watch-and-Wait as a Therapeutic Strategy in Rectal Cancer. Curr Colorectal Cancer Rep. 2018;14(2):37-55. doi: 10.1007/s11888-018-0398-5.

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

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

-

Disclosure

There is no any conflict of interest in this study

Introduction

Gastric injury induces metaplasia is based on parietal cells loss and reprogramming chief cells into proliferative, mucin-rich spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Previously, we demonstrated that parietal cell-selective Slc26a9 deficiency in mice promotes the development of SPEM and progress to gastric intraepithelial neoplasia in mice (Liu et al., Cellular oncology; 2022; Deng et al., DDW2023). However, the exact role of Slc26a9 in injury-induced metaplasia is need further investigated.

Aims & Methods

We used immunostaining to characterize the expression pattern of Slc26a9 during murine gastric development, homeostasis, and injury in homeostasis, after conditionial genetic deletion of Slc26a9. Furthermore, to reveal the functional role of Slc26a9, Injury-induced metaplasia was established in Slc26a9^fl/fl mice and Slc26a9^fl/fl/Atp4b-Cre mice with high-dose tamoxifen.

Results

Mice with parietal cell selective Slc26a9 deficiency first developed spontaneous parietal cell damage, which subsequently led to SPEM. Parietal cell injury was associated with the release of typical pyroptosis factors, including NRLP3, Caspase-1, ASC, GasderminD, IL-1β and IL-18. At the same time, SLC26A9 colocalized with caspase1, NLRP3, GSDMD, and NLRP3 and GSDMD, and produced a large number of reactive oxygen species (ROS), markers of mitochondrial damage, thereby expanding membrane perforation of GSDMD-N fragments and amplifying inflammasome-mediated parietic cell pyrodeath. At the same time, electron microscopy showed that after the knockout of the Slc26a9 gene, the mitochondria of the murine wall cells were obviously swollen, the cell membrane structure was blurred and damaged, the matrix was more dissolved, the ridge was broken and disappeared, and there were many bubble protrusions. This suggests that parietal cell specific SLC26A9 gene deletion may lead to parietal cell scorch death through mitochondrial damage mediated by GSDMD. However, with a large number of parietal cell damage and loss, gastric hypergastrinemia stimulates Tuft cell proliferation and migration to the gastric mucosa for colonization, and secretes a series of alarm hormones such as IL-25, IL-33, HMGB1. Moreover, ILC2 cell secretory factors such as IL-17RA and IL-17RB, GATA3, CD90, CD25 were up-regulated. M2 macrophage polarization-related markers such as Arg1, Fizz1, Ym1, Klf4 and secreted chemokines such as CCL24 and CCL22 were significantly up-regulated. The immunofluorescence staining of F4/80+ and CD163+ was significantly increased. This suggests that the spontaneous injury of parietal cells caused by the deletion of SLC26A9 gene in gastric parietal cells may lead to gastric dysfunction (hypoacid and hypergastrinemia) and mucosal epithelial injury, which may promote the occurrence of SPEM through IL-25 mediating the activation of ILC2 cells to regulate the cellular immune mechanism of macrophage M2 polarization.

Conclusion

Slc26a9 target deletion in parietal cells leads to spontaneous damage and scorch death of parietal cells, which is the core target and cell origin of initiating SPEM. After parietal cell specific Slc26a9 gene deletion leads to spontaneous injury of parietal cells, gastric dysfunction and mucosal injury result in the release of alarm hormone IL-25, which promotes the development of SPEM by activating IL-25-ILC2-macrophage M2 polarization axis. Slc26a9 plays an important protective role in stabilizing gastric epithelial cell differentiation and gastric mucosal immune homeostasis.

Disclosure

No conflict of interest