Introduction

H. pylori infection can remain after several eradication attempts. The objective of this study was to evaluate the effectiveness of the sixth-line rescue treatment in Europe.

Aims & Methods

Systematic and prospective registry on the clinical management of H. pylori infection. All cases with six eradication attempts registered in AEG-REDCap up to December 2022 were evaluated. The modified intention-to-treat (mITT) and per-protocol (PP) effectiveness was analysed.

Results

Overall, 81 patients were included, mainly from Spain (44% of cases), Italy (26%) and the United Kingdom (17%). The mean age was 52 years, with 52% women and 1.2% of patients allergic to penicillin. Culture was performed in 26 cases (32%), of which: 13 (50%) had bacterial antibiotic resistance to clarithromycin, 12 (46%) to nitroimidazole, and 8 (31%) to quinolones. In addition, 8 (35%) patients had dual resistance (both to clarithromycin and metronidazole) and 7 (27%) triple resistance (also to levofloxacin). Twenty-two different therapeutic combinations were used, most of them prescribed for 14 days (57%) and with low doses (39%) of PPIs. The most frequent treatments were: quadruple bismuth-tetracycline-metronidazole prescribed as three-in-one single-capsule (17%), triple amoxicillin-rifabutin (15%), quadruple bismuth-furazolidone-amoxicillin (11%), triple amoxicillin-levofloxacin (7.4%), and classical quadruple bismuth-tetracycline-metronidazole (6.2%). The highest eradication rates (mITT) were achieved with the single-capsule (77%) and with the quadruple therapy with bismuth-furazolidone-amoxicillin (67%). Overall effectiveness was 53%, both by mITT and PP analyses. Additional information on effectiveness, tolerability, compliance, and prior therapies is shown in the table.

Conclusion

Sixth-line eradication treatments in Europe obtain suboptimal eradication rates. The only therapies that reach acceptable outcomes are the bismuth quadruple therapies with either tetracycline-metronidazole (single-capsule) or with furazolidone-amoxicillin.

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

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.

Clinical Case Summary

A 65-year-old man was admitted to our emergency department presenting with intermittent abdominal distension and difficulty in defecation for over a month, and absence of passage of stool and gas for 3 days. Soft tissue masses of sigmoid colon wrapping the left ureter on abdominal CT and a large nodular neoplasm in the sigmoid colon on colonoscopy were observed. Advanced colon cancer was highly suspected. However, we made sixes times biopsy totally and found no evidence of malignancy. Histopathology only showed moderate to severe chronic mucosal inflammation. We finally performed the subtotal colectomy and the histopathology of the excised colon showed us an unexpected finding: Schistosoma japonicum ova.
According to the data published by WHO in 2020, schistosomiasis has been reported in 78 countries worldwide, resulting in an estimated 240 million deaths¹. These highlight the significance of schistosomiasis eradication. Further history taking observed that the patient swam in the Baishui River, a tributary of Yangtze River, an endemic area of schistosomiasis, in recent four years of summer vacation.
During endoscopic examinations, patients may have characteristic scattered yellow nodules, while non-specific mucosal congestion, edema, thickening, ulcers, and polyps may be commonly observed. Therefore, misdiagnosis of intestinal schistosomiasis is common, with the rate of 30.3%^2,3. As we know, we made the first report of intestinal schistosomiasis infiltrating peritoneum and ureter, mimicking advanced colon cancer or Crohn’s disease. This highlights the importance of multi-site and deep biopsies or even surgery for the diagnosis of colonic neoplasm, especially when Schistosoma ova are distributed focally in submucosal area. Moreover, Schistosoma are far from eradication. Physicians should include schistosomiasis as a common differential diagnosis of colonic neoplasm. Detailed history taking of travel and migration is necessary in these patients.

References

(1) Díaz, A. V.; Walker, M.; Webster, J. P. Reaching the World Health Organization Elimination Targets for Schistosomiasis: The Importance of a One Health Perspective. Philos Trans R Soc Lond B Biol Sci 2023, 378 (1887), 20220274. https://doi.org/10.1098/rstb.2022.0274.
(2) Yang, Y.; Wang, X.-Y.; Duan, C.; Wang, Z.-J.; Sheng, H.-Y.; Xu, X.-L.; Wang, W.-J.; Yang, J.-H. Clinicopathological Characteristics and Its Association with Digestive System Tumors of 1111 Patients with Schistosomiasis Japonica. Sci Rep 2023, 13 (1), 15115. https://doi.org/10.1038/s41598-023-42456-9.
(3) Cai, L.; Chen, Y.; Xiao, S.-Y. Clinicopathologic Features of Chronic Intestinal Schistosomiasis and Its Distinction From Crohn Disease. Am J Surg Pathol 2021, 45 (3), 430–438. https://doi.org/10.1097/PAS.0000000000001594.

Clinical Case Summary

We present a rare case of protein losing gastropathy.A 60-year-old female presented to our clinic with 10 years history of intermittent dyspepsia with no alarm features and peripheral oedema for 6 months.Physical examination was unremarkable except mild bilateral pitting oedema.Pertinent investigations suggested normal albumin,urine analysis,renal&liver profiles and a normal echocardiogram.Subsequent testing with esophagogastroduodenoscopy(EGD) for dyspepsia showed hypertrophied mucosal folds predominantly in gastric corpus while sparing the antrum.Full thickness biopsies were taken and sent for histopathology with differentials of Lymphoma,adenocarcinoma,sarcoidosis and Menetrier’s disease.Stool antigen for Helicobacter Pylori(H.Pylori)thereafter,was positive while Contrast enhanced CT abdomen was consistent with mildly thickened gastric walls.Histological examination demostrated foveolar hyperplasia,elongated gastric pits and cystically dilated gastric glands without any features of malignancy.Hence a diagnosis of Menetrier’s disease(underlying H.Pylori) was made.
Patient then had H.Pylori eradication therapy as well as a diet rich in medium-chain fatty acids and proteins.H.Pylori eradication was confirmed.6 months follow up revealed partial resolution of her symptoms but no change in endoscopic findings.Patient could not undergo further treatment with biologics(cetuximab)due to financial constraints and octreotide for its local unavailability.She is now on a yearly endoscopic surveillance for future high risk of gastric malignancies.

References

​​Fig1A.Haematoxylin & Eosin staining shows foveolar & mucous cell hyperplasia,elongated gastric pits and lymphocytic infiltration.
Fig1B.Haematoxylin & ​Eosin staining shows cystic dilation of gastric glands
1.Pepa P, Uehara T, Wonaga A, Redondo A, Avagnina A, Mazzocchi O, Antelo P, Waldbaum C, Sorda J. Menetrier's disease. A diagnostic and therapeutic challenge. Medicina (B Aires). 2021;81(3):470-473. English. PMID: 34137712.
2.Gore M, Bansal K, Jadhav N. Menetrier Disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan– [updated 2023 Jun 25].

Disclosure

No conflicts

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

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.