Introduction

Hepatocellular carcinoma (HCC) is the most common primary malignant liver cancer globally and ranks as the third leading cause of cancer-related mortality. Treatment with immune checkpoint inhibitors (most commonly atezolizumab in combination with bevacizumab) is the most effective first-line systemic therapy for patients with advanced HCC. Since it is a new method of treatment, there is little clinical data on the use of this combination of drugs in practice (outside of prospective studies). This study aims to present the clinical outcomes of patients with HCC who underwent immunotherapy at our center over the past three years.

Aims & Methods

In this retrospective observational study, we included patients treated with the atezolizumab and bevacizumab combination between March 2020 and September 2023. Demographic information, general physical assesments, disease etiology, disease staging, liver cirrhosis status, portal hypertension and laboratory values (aminotransferases and total bilirubin) were collected. Adverse events were analyzed according to the Common Terminology Criteria (CTCAE). Descriptive statistics and survival analysis were performed using Statistical Package for the Social Sciences (SPSS) version 22.

Results

53 HCC patients received atezolizumab and bevacizumab in studied time period, 8 (15.1%) females and 45 (84.9%) males. The median age at the initiation of immunotherapy was 68 years (range 41 – 84 years). Thirteen patients (24.5%) had esophageal varices prior to immunotherapy, with three (5.6%) requiring ligation. The majority of patients had liver cirrhosis A 27 (50.9%) according to Child Pugh criteria, a minority B (9.4%), and 21 patients (39.6%) were without cirrhosis. The primary causes of the disease were alcohol (51.6%), metabolic dysfunction-associated steatotic liver disease (MASLD) (16.1%), hepatitis C virus (12.9%), hepatitis B virus (6.5%), and hemochromatosis (3.2%). Stage C HCC, according to The Barcelona Clinic Liver Cancer, World Health Organization (WHO) performance status 0, and absence of macrovascular invasion and extrahepatic spread were predominant at treatment initiation. Grade I or II adverse events occurred in almost all patients (98.1%). Severe adverse events were present in 36 patients (67.9%). Due to severe side effects, 8 (15.1%) patients discontinued treatment, 2 (3.8%) died due to treatment related complications (encephalitis and bleeding from esophageal varices). Treatment was modified in 21 (39.6%) patients due to adverse events. The estimated median survival was 15.7 months.

Conclusion

The majority of patients with unresectable HCC, treated with a combination of atezolizumab and bevacizumab immunotherapy, experienced adverse events, primarily grades I-II. The immunotherapy combination proved to be more effective in patients with viral etiology of liver cirrhosis. The estimated median survival was 15.7 months. This combination of immunotherapy has been demonstrated to be a safe and effective treatment method. Currently, there is limited data regarding the utilization of this treatment in standard clinical practice and our data aligns reasonably well with the findings of the registration study.

References

1. McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of Hepatocellular Carcinoma. Hepatology. 2021 Jan;73 Suppl 1(Suppl 1):4–13.
2. Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022 Mar;76(3):681–93.
3. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894–905.
4. Lee YC, Huang WT, Lee MY, Tsao CJ, Feng YH. Bevacizumab and Atezolizumab for Unresectable Hepatocellular Carcinoma: Real-world Data in Taiwan-Tainan Medical Oncology Group H01 Trial. In Vivo. 2023;37(1):454–60.
5. Himmelsbach V, Pinter M, Scheiner B, Venerito M, Sinner F, Zimpel C, et al. Efficacy and Safety of Atezolizumab and Bevacizumab in the Real-World Treatment of Advanced Hepatocellular Carcinoma: Experience from Four Tertiary Centers. Cancers (Basel). 2022 Mar 28;14(7):1722.
6. de Castro T, Jochheim LS, Bathon M, Welland S, Scheiner B, Shmanko K, et al. Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience. Ther Adv Med Oncol. 2022;14:17588359221080298.

Introduction

The urea breath test (UBT) is the clinic's most popular and accurate non-invasive diagnostic method for H. pylori infection. Yet, it is time-consuming and unavailable to some individuals. The oral rapid urease test (RUT) is an emerging non-invasive convenience method but lacks clinical data support.

Aims & Methods

A double-center, double-blind, methodological comparative design experiment is invited to evaluate the consistency of the oral RUT with UBT. 247 participants were enrolled. Their Dental plaque and tongue coating samples were collected, blind and tested with RUT.

Results

The significant association between the RUT and UBT was analyzed.A total of 247 participants were included in the study. The oral RUT showed a high level of agreement with the UBT. The sensitivity of the test reagent was 98.63% (95% CI: 92.64%, 99.76%), and the specificity was 96.34% (95% CI: 92.25%, 98.31%). The overall conformity rate was 97.05% (95% CI: 94.03%, 98.56%). The positive predictive value was 92.31%, and the negative predictive value was 99.37%. The positive likelihood ratio was 26.96, and the negative likelihood ratio was 0.01. The Kappa value was 0.97.

Conclusion

The efficacy of oral RUT for Helicobacter pylori infection diagnosis is extremely consistent with the UBT.

Introduction

Helicobacter pylori (H.pylori) infection is the main risk factor for gastric cancer. Infection leads to chronic inflammation and gastric gland hyperplasia. We found that infection induces alterations in the stromal niche, such as inhibited secretion of BMP ligands and increased expression of BMP inhibitors. BMP signaling is known to be involved in differentiation of base progenitor cells into pit secretory cells. However, whether it plays a role in regulating mucosal antimicrobial defense is still unknown and we now investigate how the downregulation of BMP signaling affects mucosal inflammatory responses.

Aims & Methods

Exploiting in vivo murine models as well as in vitro assays, we aim to investigate how the downregulation of epithelial BMP signaling affects mucosal homeostasis.
3D gastric organoids were used to explore the role of BMP in epithelial responses to microbial proteins (qPCR, Western Blotting). The effects of epithelial BMP downregulation and stromal Il1r1 signaling were investigated by exploiting conditional knockout mice (Axin2CreERT2-Bmpr1afl/fl or Bmpr1a KO; Col1a2CreERT2-Il1r1fl/fl or Il1r1 KO) either uninfected or infected with H.pylori PMSS1. Tissue samples were analyzed via immunofluorescence, RNA-in situ hybridization and gene expression analysis (qPCR, whole transcriptome). 2D primary murine stromal cell culture were exploited to investigate stromal responses to inflammatory triggers.

Results

Exploiting 3D organoids, we demonstrate that epithelial cells activate NF-κB signaling in response to microbe-derived proteins, while this effect is inhibited upon BMP signaling activation. In vivo, inhibition of BMP signaling in the epithelium via knockout of Bmpr1a (Bmpr1a KO) not only causes gland hyperplasia but also strongly enhances inflammation at the pit of gastric glands, where it is absent in mice with functional BMP signaling. We explore the consequences of increased inflammation upon epithelial Bmpr1a KO, demonstrating via whole transcriptome analysis that this is linked to enhanced antimicrobial tissue responses and that KO mice show reduced H.pylori colonization. Moreover, we discover that the influx of IL-1β producing cells observed upon BMP signaling downregulation has an impact on stromal cells, which in turn produce pro-regenerative factors causing epithelial reprogramming into a highly proliferative fetal-like regenerative state. We demonstrate that Il1r1 KO mice, where stromal cells lack the ability to respond to IL-1β, do not show fetal-like reprogramming and are more colonized by H.pylori.

Conclusion

Chronic H.pylori infection causes tissue reprogramming into a fetal-like state via a crosstalk between epithelial, stromal and immune cells. This state is linked to an enhanced proinflammatory response, increased proliferation and boosters antimicrobial defense. We propose that long-term activation of this state may enhance the risk for malignant transformation.

Clinical Case Summary

Introduction: Kaposi sarcoma is the most common digestive malignancy in Human Immunodeficiency Virus (HIV)-positive patients, but it can also occur in HIV-negative individuals. It is a low-grade vascular tumor associated with Human Herpes Virus-8 (HHV-8) and can appear in immunosuppressed patients. Lesions can develop on the skin, but they could also be found in internal organs and lymph nodes.
Case-report: A 61-year-old Caucasian female with alcoholic liver cirrhosis and diabetes mellitus presented in the Dermatology Department with multiple painless red-to-purple papular nodules across the thorax, cervical area, limbs, and face. Skin biopsies from the posterior cervical area and internal part of the right foot revealed a well-defined nodular dermal tumor with submucosal vascular spindle cells forming slits containing red blood cells and low mitotic activity. Immunohistochemistry confirmed CD34, CD31, HHV-8, and Ki67>30% expression, indicative of cutaneous Kaposi sarcoma. HIV serological tests were negative. Further assessments performed in the Gastroenterology Department established decompensated liver cirrhosis. Moreover, upper digestive endoscopy revealed esophageal varices, portal hypertension gastropathy, along with multiple umbilicated nodules with central ulcerations in the gastric fundus and body. Biopsy samples from these lesions described histopathological findings suggestive of Kaposi sarcoma, while immunostaining for HHV-8 and CD31 was positive. Proposed systemic chemotherapy was declined by the patient. Tumors of the gut with spindle-shaped cells such as leiomyomas, rhabdomyosarcomas, or gastrointestinal stromal tumors must be considered in the differential diagnosis of Kaposi sarcoma.
Conclusion: Kaposi sarcoma can develop in HIV-negative immunosuppressed patients, with conditions such as liver cirrhosis and HHV-8 infections, potentially affecting the digestive tract.

References

1. Xu H, Edwards JR, Espinosa O, Banerji S, Jackson DG, Athanasou NA. Expression of a lymphatic endothelial cell marker in benign and malignant vascular tumors. Hum Pathol 2004;35:857–861.
2. Rossi S, Orvieto E, Furlanetto A, Laurino L, Ninfo V, Dei Tos AP. Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody. Mod Pathol 2004;17:547–552.
3. Antman K, Chang Y. Kaposi's sarcoma. N Engl J Med. 2000;342:1027–1038.
4. Huang WY, Pantanowitz L, Dezube BJ. Unusual sites of malignancies: CASE 3. AIDS-related Kaposi's sarcoma of the gastrointestinal tract. J Clin Oncol. 2005;23:2098–2099.
5. Arora M, Goldberg EM. Kaposi sarcoma involving the gastrointestinal tract. Gastroenterol Hepatol (N Y). 2010 Jul;6(7):459-62. PMID: 20827371; PMCID: PMC2933764.

Disclosure

No conflict of interest.

Introduction

Screening programmes for gastric cancer are currently being researched in Europe as part of the TOwards GAstric Cancer Screening Implementation (TOGAS) project (1). A ‘screen & treat’ approach for Helicobacter pylori (H. pylori), is one such strategy being assessed as part of a primary preventative measure. In order for such a programme to be viable, the availability of an effective treatment is paramount. Given the rising rates of antimicrobial resistance worldwide, careful consideration must be given to prescribing first-line treatment with the highest efficacy. This interim report evaluates key performance measures in the treatment of H. pylori within the Irish arm – representing the Western European cohort - of the TOGAS pilot screening programme.

Aims & Methods

This interim data evaluates the efficacy of 10-day treatment with single capsule combination therapy: Bismuth subcitrate 140mg/Metronidazole 125mg/Tetracycline 125mg, three tablets, four times daily (PYLERA, Juvise pharmaceuticals) with a high-dose proton pump inhibitor (Esomeprazole 40mg twice daily).
Secondary outcome measures include;

1. Treatment acceptance rate
2. Side-effect profile
3. Adverse events

3030 individuals aged 30-34 years were invited to undergo screening for H. pylori through their general practitioner or workplace in the period January 24-March 25. Those who tested positive on both serology (BIOHIT H. pylori IgG antibody) and 13-C urea breath test (IR Force 200, Richen Medical) were offered treatment. Treatment consisted of 10-day combination therapy (PYLERA) and a high-dose proton pump inhibitor (PPI). Eradication confirmation with a 13-C UBT was offered a minimum of 6 weeks post-treatment. Demographics, risk factors for infection, treatment effectiveness and side effect profile were recorded. Stata was used for statistical analysis. χ² test was used for comparison of categorical variables (significance level p<0.05).

Results

464 asymptomatic individuals were enrolled. The median age was 32; 48%(n=223) were male. 11%(n=50) tested positive on both serology and 13-C UBT. Those who tested positive were more likely to be male [64%] (p < 0.02), a history of current or previous smoking was found to be nonsignificant (34%, p <0.9). 96%(n=48) of positive participants consented to treatment; 2 were excluded from receiving treatment due to pregnancy. Among those treated, 96% (44/46) reported adherence rates of >90%. In those reporting compliance rates <90 %, side effect profile was the leading cause of non-compliance. Side effects were reported by 24% (11/46) of participants. These were predominantly gastrointestinal side effects and reported as mild-moderate in severity, 6% discontinued treatment on account of them (n=3). All symptoms resolved after cessation. No serious adverse events occurred. Post-treatment, a 13-C UBT was completed in 80% (n=37) of treated individuals. Eradication rates were 97% (36/37) in the per-protocol group and 89% (33/37) in the intention-to-treat group. Treatment discontinuation due to side effects was the leading cause of treatment ‘failure’. In those requiring 2^nd line therapy (n=4), levofloxacin-based quadruple therapy was found to be successful in 66%(2/3) of those who completed eradication follow-up.

Conclusion

Single capsule combination therapy and high-dose PPI achieved eradication rates of >90% in the per-protocol group. No serious adverse events occurred secondary to treatment. These interim results indicate that 10-day combination therapy serves as an effective first-line therapy for future population-based screening programmes in a European population.

References

1. Commission E. TOGAS - Towards Gastric Cancer Screening Implementation in the European Union: European Commission; 2023 [Available from: https://health.ec.europa.eu/non-communicable-diseases/cancer/europes-beating-cancer-plan-eu4health-financed-projects/projects/togas_en.

Disclosure

Dr. Deane reports receipt of research funding support from EU4 Health grant GA number: 101101252. Juvise pharmaceuticals provided PYLERA for this branch of the study.

Introduction

Europe’s Beating Cancer Plan identified the urgent need for a gastric cancer screening strategy. In response, the TOGAS consortium (TOwards GAstric cancer Screening in the European Union) was established to evaluate different methods for gastric cancer prevention and detection within Europe(1). One such approach involves population-based screening of young adults for Helicobacter pylori (H.pylori) as a primary preventative strategy.

Aims & Methods

The pilot study aimed to assess the feasibility of screening asymptomatic 30-34 year olds for H.pylori. Key outcome measures included:
1) Response rate
2) Seropositivity
3) Treatment acceptance rate
4) Treatment effectiveness
Methods: Individuals aged 30-34 years were invited to participate in free screening via GP practices or occupational-based screening programmes in the period January 2024- March 2025. Invitations were distributed through email or text message at the discretion of the recruitment stream. Exclusion criteria included prior history of treatment of H. pylori or gastrectomy. Those who tested positive on serology (BIOHIT H. pylori IgG antibody, antibody titer >30 IU/ml) were offered confirmatory 13-C urea breath testing (Richen IR Force 200). Positive participants were offered treatment with a 10-day regimen of single capsule combination therapy (Bismuth subcitrate 140mg/Metronidazole 125mg/Tetracycline 125mg, three tablets, QDS; PYLERA, Juvise pharmaceuticals) + Esomeprazole 40mg BD. Eradication confirmation was offered a minimum of 6 weeks post-treatment. Demographics, risk factors, and treatment effectiveness were recorded.
The calculated sample size for statistical significance at a 95% confidence interval with a presumed prevalence rate of 30% was 323. The Mann-Whitney U-test was used for comparison of continuous variables, and the Chi² test for categorical variables (significance set at p<0.05).

Results

3030 invites were distributed (80% GP practices, 20% occupation-based). 20%(n=604) of recipients expressed interest in participating. Among these; 5%(n=31) were excluded and 18%(n=109) refused or ceased responding. 464 consented to and completed the study. The median age of participants was 32, 48%(n=223) were male. 15% (n=75) of those who underwent serology testing were seropositive. 97% agreed to have a confirmatory 13-C UBT, of which 50/73 (66%) tested positive. The median titre in this dual positivity group was 109 IU/mL [range 40-142], compared to 37 IU/mL [range 32-148 IU/ml] in the 13-C UT negative group. Overall, the true ‘positivity’ rate among those who agreed to screening was 11%. 96%(48/50) of positive participants agreed to treatment, a further 2 were excluded due to pregnancy. Among those treated, 96% (44/46) reported >90% adherence. 1^st line eradication rates, confirmed by a 13-C UBT, were 97%(36/37) in the per-protocol group and 89%(33/37) in the intention-to-treat group. Side effects were reported by 24%, the majority of which were GI. 4 patients required 2^nd line therapy due to early discontinuation or poor compliance, 1 failed 2^nd line therapy on follow-up eradication confirmation.

Conclusion

These interim results indicate that a population-based H.pylori screening approach is feasible within an Irish population. Despite a decreasing worldwide prevalence, infection remains a persistent issue. Although initial response rates to screening are modest, this is a novel pilot programme and reflects trends seen in the early phases of other national screening programmes, such as the colorectal cancer screening. As public awareness increases, higher engagement rates are anticipated.

References

1. Commission E. TOGAS - Towards Gastric Cancer Screening Implementation in the European Union: European Commission; 2023 [Available from: https://health.ec.europa.eu/non-communicable-diseases/cancer/europes-beating-cancer-plan-eu4health-financed-projects/projects/togas_en.

Disclosure

Dr. Deane reports receipt of research funding support from EU4 Health grant GA number: 101101252

Introduction

Approximately 15-19% of patients suffering from irritable bowel syndrome (IBS) have an eating disorder (ED) based on a screening score or dietary assessment (1). Avoidant/restrictive food intake disorder (ARFID), a long-recognised eating disorder in children, is now recognised in adults. In a Swedish study, 13.2% of patients suffering from IBS reported severe dietary avoidance or restriction, suggestive of ARFID (2). A screening questionnaire for this disorder has recently been validated in French (NIAS-Fr, for Nine Item ARFID Screen in French) (3).

Aims & Methods

This study aims to assess the prevalence of ARFID in IBS in France, by comparing the NIAS-Fr questionnaire and the assessment by a specialised dietitian, and to look for links between its presence and the clinical phenotype of patients. This study was conducted between February and September 2024 in consecutive patients suffering from IBS and evaluated in a multidisciplinary day hospital structure. Clinical characteristics (age, gender, BMI, IBS subtype and its severity [IBS-SSS], presence of functional dyspepsia, diet and disease duration) and presence of ARFID (clinically or one abnormal NIAS-Fr subscale) were collected. A dietitian assessed the presence of “clinical ARFID”. The NIAS subscales allow for the diagnosis of patients as “picky eaters” (score ≥10), with “poor appetite” (score ≥9) and/or with a “fear of eating” (score ≥10). Patients with a history of ED diagnosed by a psychiatrist and/or an abnormal ED screening score (SCOFF ≥ 3 and/or global EDE-Q8 ≥ 4.0) were excluded from the analysis.

Results

Of the 95 patients with IBS according to Rome IV, 55 (57.9%) had at least one positive NIAS-Fr subscale, with 10 (10.5%) having an abnormal “picky eater” subscale, 16 (16.8%) an abnormal “poor appetite” subscale, and 49 (51.6%) an abnormal “fear of eating” subscale. Of these 95 patients, 15 were excluded from the analysis because of a history of eating disorders or an abnormal screening score. We therefore included 80 patients for analysis (77.5% women; mean age 48.5 ± 16.8 years, BMI 22.6 ± 4.6 kg/m²; 40.0% IBS-D, 38.8% IBS-C, and 20.0% IBS-M; 51.3% had associated dyspepsia; 62.5% were on a special diet at the time of assessment). The mean IBS-SSS score was 319.5 ± 88.2 points (severe forms in 61.2%). Among these 80 patients, 43 (53.8%) had at least one positive NIAS-Fr subscale, including 10.0% of "picky eaters," 16.3% of "poor appetite," and 48.8% of "fear of eating." Patients with at least one positive NIAS-Fr subscale had more frequent functional dyspepsia than those with a negative NIAS (65.1 vs. 35.1%, p = 0.013), but there were no differences in the other parameters assessed. According to the dietitian's assessment, 19 (23.8%) patients in our cohort had clinical ARFID, i.e., 44.2% of those with at least one positive NIAS-Fr subscale. In an IBS population, the specificity of the NIAS-Fr questionnaire for diagnosing clinical ARFID was 55.8% (95% CI: 41.1-69.6). None of the assessed parameters distinguished patients with and without clinical ARFID (p > 0.05).

Conclusion

ARFID symptoms are found in more than half of IBS patients treated in a tertiary care centre based on an abnormal NIAS-Fr screening questionnaire, after excluding other eating disorders. These patients frequently have associated functional dyspepsia and a normal BMI. Based on a dietary assessment, clinical ARFID is found in approximately one-quarter of IBS patients. The specificity of the NIAS-Fr in IBS is too low to allow a diagnosis of ARFID in this population.

References

(1) Wuestenberghs et coll. Intérêt du dépistage des troubles du comportement alimentaire au cours du syndrome de l’intestin irritable. JFHOD 2024 (number 000694)
(2) Melchior et coll. Food Avoidance and Restriction in Irritable Bowel Syndrome: Relevance for Symptoms, Quality of Life and Nutrient Intake. Clin Gastroenterol Hepatol. 2022;20(6):1290-1298.e4.
(3) Van Ouytsel et coll. Translation of the nine item avoidant/restrictive food intake disorder screen (NIAS) questionnaire in French (NIAS-Fr). Neurogastroenterology & Motility 2024 ; 36 (4) : e14757.

Disclosure

Nothing to disclose.