Clinical Case Summary

Background: Eosinophilic oesophagitis (EoE) is a type-2 mediated chronic inflammatory disease affecting the oesophagus, characterized by symptoms related to oesophageal dysfunction, such as dysphagia or persistent reflux symptoms despite optimal PPI therapy, and an elevation of eosinophil counts at different levels of the digestive tract wall, in the absence of other causes of eosinophilia^1,2.
A relationship has been found between EoE and allergic comorbidities and a certain degree of heredity in the pathogenesis of the disease^3,4,5. Histologic diagnosis: ≥15 eosinophils /HPF^6,7,8.
Case report: We evaluated a 28-year-old woman for suspected oesophageal rupture. In anamnesis: hypothyroidism, lactose intolerance, milk protein allergy.
On arrival, the patient complained of retrosternal pain, dysphagia, emesis, and sialorrhea. Immediate EGDS found oesophageal fissuration, extending 26 to 33 cm from dental arch, with rigidity of viscera and vertical grooves from middle oesophagus to cardia (Image 1, 2); multiple biopsies were performed in proximal and distal oesophagus for suspected EoE; naso-digiunal feeding tube was placed for proper feeding and the patient was kept on nihil per os. Histology confirmed the clinical suspicion of eosinophilic esophagitis. After 3 days, progressive reintroduction of diet per os was carried out. Upon histological confirmation, steroid therapy and PPI were set. A chest-CT scan, with and without iv and oral contrast showed spillage of contrast from the oesophageal lumen, as for mucosal tear, without clear signs of perforation (Image 3). Upon remission of symptoms, the patient was discharged with a soft diet, full dose proton pump inhibitors an systemic steroid on a sliding scale. Oral Budesonide was introduced in one week when the systemic steroid was suspended. One month after discharge, the patient had a complete remission of symptoms. Three months endoscopic follow-up confirmed total regression of the lesion (Image 4).

References

1. Hahn J.W., et al. Global Incidence and Prevalence of Eosinophilic Esophagitis, 1976–2022: A Systematic Review and Meta-analysis. CGH 2023 doi: 10.1016/j.cgh.2023.06.005
2. Dellon E.S. et al. International Consensus Recommendations for Eosinophilic Gastrointestinal Disease Nomenclature. CGH Off. Clin. Pract. J. Am. Gastroenterol. Assoc. 2022;20:2474–2484.e3. doi: 10.1016/j.cgh.2022.02.017.
3. Guajardo J.R., et al. Eosinophil-associated gastrointestinal disorders: A world-wide-web based registry. J. Pediatr. 2002;141:576–581. doi: 10.1067/mpd.2002.127663.
4. Díaz del Arco C., et al. Eosinophilic colitis: Case series and literature review. Pathol. Res. Pract. 2018;214:100–104. doi: 10.1016/j.prp.2017.09.029.
5. Visaggi P., Savarino E. Et al Six-Food Elimination Diet is Less Effective During Pollen Season in Adults with Eosinophilic Esophagitis Sensitized to Pollens. Am. J. Gastroenterol. 2023 doi: 10.14309/ajg.0000000000002357.
6. Lucendo A.J. et al. Guidelines on eosinophilic esophagitis: Evidence-based statements and recommendations for diagnosis and management in children and adults. UEG J. 2017;5:335–358. doi: 10.1177/2050640616689525
7. Hirano I., et al. AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis. Gastroenterology. 2020;158:1776–1786. doi: 10.1053/j.gastro.2020.02.038.
8. de Bortoli N., et al. Eosinophilic esophagitis: Update in diagnosis and management. Position paper by SIGE Dig. Liver Dis. 2017;49:254–260. doi: 10.1016/j.dld.2016.11.012

Disclosure

None

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

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.

Clinical Case Summary

Endoscopic full-thickness resection (eFTR) is an emerging technique that enables effective and safe management of complex colorectal (CR) lesions. In recent years, eFTR has been described as an alternative to surgery in selected patients, namely for scars aiming to exclude residual tumors after non-curative endoscopic resection. We present a case of eFTR due to imaging suspicion of intraparietal colorectal recurrence without endoscopic findings.
A 41-year-old woman with Lynch syndrome (dMLH1) and a history of rectal adenocarcinoma underwent anterior resection of the rectum and adjuvant chemoradiotherapy at the age of 20. Afterwards endoscopic surveillance was initiated. At the age of 39, she presented with a suspicious lesion (Paris 0-Is+IIa, NICE 2, JNET2B), 16mm, in the hepatic angle, and underwent enbloc endoscopic mucosal resection. Histopathological analysis revealed a low-grade invasive colorectal carcinoma (CRC) with deep invasion of the submucosa (vertical R1). After a multidisciplinary meeting, complementary surgery was proposed but the patient refused, maintaining close surveillance. Two subsequent endoscopic revisions and two computed tomography (CT) scans showed no signs of macro or microscopic recurrence, even after extensive biopsies of the colonic scar. However, a CT scan 20months post-resection showed a 2cm parietal thickening in the hepatic angle. Suspecting parietal tumor recurrence without superficial endoscopic findings, a transmural endoscopic resection using FTRD® of the scar was performed. Histology revealed no tumor recurrence.
Transmural evaluation of the scar after noncurative endoscopic resection of T1 CRC, whether for excluding residual tumor or during surveillance to exclude recurrence, represents a promising indication for eFTR. This technique has demonstrated to be a safe and effective therapeutic alternative for this new indication, avoiding surgery and its associated morbidity and mortality.

References

Aslanian HR, Sethi A, Bhutani MS, Goodman AJ, Krishnan K, Lichtenstein DR, et al. ASGE guideline for endoscopic full-thickness resection and submucosal tunnel endoscopic resection. VideoGIE 2019;4:343–50. https://doi.org/10.1016/j.vgie.2019.03.010.
Gijsbers K, Laclé M, Elias SG, Backes Y, Bosman J, van Berkel A. Full-Thickness Scar Resection After R1 / Rx Excised T1 Colorectal Cancers as an Alternative to Completion Surgery : Official journal of the American College of Gastroenterology | ACG. Am J Gastroenterol 2022;117:647–53. https://doi.org/10.14309/ajg.0000000000001621.
Pimentel-Nunes P, Libânio D, Bastiaansen BAJ, Bhandari P, Bisschops R, Bourke MJ, et al. Endoscopic submucosal dissection for superficial gastrointestinal lesions: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022. Endoscopy 2022;54:591–622. https://doi.org/10.1055/a-1811-7025.

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.