Introduction

The low fermentable oligosaccharide, disaccharide, monosaccharide and polyol diet (LFD) has been purported as a first line therapeutic treatment for the management of irritable bowel syndrome (IBS)^1,2. Despite the extensive research supporting the efficacy of the LFD^{3 4}, there are few studies exploring the lived experience of people with IBS undertaking a dietitian-led three-phase LFD.

Aims & Methods

This study aimed to explore people’s expectations of and experience with each phase of the LFD, and identify barriers and enablers to successfully completing each phase. A descriptive, qualitative design employed semi-structured interviews with adults with IBS who undertook all or part of a dietitian-led research study on predictors of response to a LFD. Participants underwent LFD restriction, reintroduction and personalisation between October 2020 and April 2022. Interviews examined expectations and experiences of the LFD process, and barriers and enablers to undertaking and completing each phase. Sociodemographic and IBS characteristics were also collected. Thematic analysis summarised key themes.

Results

Seventeen people (32%, 17/53 response rate) aged 37.5 ± 14 years (88% female) completed interviews, of whom 76% (13/17) completed all three phases of the LFD. Duration of experiencing IBS symptoms ranged from one to 40 years with 76% experiencing diarrhoea as the most predominant symptom. Four themes emerged from the data. Firstly, people presented with different IBS and healthcare experiences, and expectations of what the LFD would provide. Previous unsuccessful treatments (pre- and probiotics, gluten elimination, herbal medicine) motivated people to undertake the LFD. Secondly, people’s expectations of outcomes within each phase varied and was related to their symptom response. People expected symptom resolution during the restriction phase and were disappointed that symptoms were not entirely alleviated. Symptoms during the reintroduction phase were a barrier to continuing challenges for some but others felt that symptoms assisted in identifying trigger foods. Despite overall reductions in symptoms during each phase, a residual frustration was felt as symptoms were not eliminated on completion of personalisation. Thirdly, the three-phase process required significant planning, effort and self-efficacy. Ability to adhere to personal tolerance levels of fermentable carbohydrates was an enabler to successful completion of the reintroduction and personalisation phase. Environmental barriers included eating out, multi-person households and altering meals to suit family mealtimes. Personal barriers included perceptions of food triggers, apprehension to try foods that had long been avoided and experiencing symptoms during the reintroduction phase. Lastly, most people incorporated learning and experiences from the LFD into daily life after reintroduction. Those with symptom improvement identified strategies to circumvent FODMAP intake in daily life and were understanding of the interplay between food, the environment and psychological factors on symptoms. Some used the LFD restriction to manage symptom exacerbations.

Conclusion

The LFD process is complex, and personal beliefs, experiences and expectations impact on adherence and completion of each phase. Further personalisation of the LFD to individual circumstances is fundamental to improving the experience and outcome of this therapeutic management strategy in people with IBS. These findings will be used to inform improved implementation to optimise peoples experience and success with the LFD.

References

¹ Clinical Decision Support Tool: IBS Treatment. (2022). Gastroenterology 163(1): 152-152 http://doi.org./10.1053/S0016-5085(22)00536-4
² Vasant, D.H., Paine, P.A., Black, C.J., Houghton, L.A., Everitt, H.A., Corsetti, M., Agrawal, A., Aziz, I., Farmer, A.D., Eugenicos, M.P, Moss-Morris, R., Yiannakou, Y & Ford, A, C. (2021). British Society of Gastroenterology guidelines on the management of irritable bowel syndrome Gut, 70(7), 1214-1240.http://doi.org/10.1136/gutjn-2021-324598
³ Black, C.J., Staudacher, H.M & Ford, A.C. (2022). Efficacy of a low FODMAP diet in irritable bowel syndrome: systematic review and network meta-analysis. Gut, 71(6), 1117-1126. doi:10.1136/gutjnl-2021-325214
⁴ Wang, J., Yang, P., Zhang, L and Hou, X. (2021). A low FODMAP diet improves the global symptoms and bowel habits of adult IBS patients: A systematic review and meta-analysis. Frontiers in nutrition, 8. http://doi.org/10.3389/fnut2021.683191

Introduction

Functional dyspepsia (FD) is a disorder of gut-brain interaction (DGBI) characterized by postprandial fullness, early satiation, epigastric pain or burning in the absence of a readily identifiable cause at upper endoscopy. Proton pump inhibitors (PPIs) are often used as a first-line treatment for FD, although their efficacy has not been convincingly established.

Aims & Methods

The aim was to investigate symptom patterns in FD patients with and without acid-suppressive therapy (PPI or H2-antagonist, H2RA) and to evaluate the use of these drugs in different patient groups. Ambulatory tertiary-care patients referred for upper gastrointestinal endoscopy were requested to fill out Rome IV gastro-duodenal questionnaires. Those fulfilling Rome IV FD criteria with a negative endoscopy were identified as FD patients and subdivided into patients on and off acid-suppressive therapy. The pattern of GI symptoms was compared between these two subgroups, using frequency thresholds from the Rome IV criteria. The chi-square or Fisher exact (when applicable) test was used to evaluate statistical significance (p<0.05).

Results

The Rome IV questionnaire was filled out by a total of 1002 patients (58% females, 48.5 ± 0.5 years, BMI 25.4± 0.5). Of these, 229 (23%, 73% females, 45.5 ± 1.1 years, BMI 23.9 ± 0.3) fulfilled the diagnostic criteria for FD. Organic findings at endoscopy included Barrett’s oesophagus (n=40, 4%), peptic ulcers (n=24, 2%), and reflux oesophagitis (n=352, 35%).
PPI/H2RA usage in FD patients was 60%, which was not significantly different from patients diagnosed with Barrett’s oesophagus (75%, p=0.07), peptic ulcer (50%, p=0.33), reflux oesophagitis (57%, p= 0.45) or the combined group with organic abnormality at upper endoscopy (46%, p=0.1). There was no significant difference (p=0.67) in PPI/H2RA usage between the EPS (epigastric pain syndrome, 55% usage) and PDS (postprandial distress syndrome, 50% usage) subgroups of FD.
The most prevalent symptoms in FD patients were postprandial fullness (76%), epigastric pain (67%) and bloating (62%). Patients on acid-suppressive therapy reported more nausea (41% vs 27%, p=0.04) and excessive belching (50% vs 36%, p=0.05) compared to patients without acid suppression. There was no significant difference in postprandial fullness (84% vs 73%, p=0.05), epigastric pain (75% vs 64%, p=0.08), heartburn (17% vs 28%, p=0.06) and bloating (70% vs 58%, p=0.06) between the two subgroups. Looking at the EPS and PDS subgroups of FD, there was a significant difference (p=0.03) in bloating between patients on (73%) and off (46%) acid suppression in the PDS subgroup of FD.

Conclusion

The cardinal symptom pattern in FD patients referred for upper endoscopy is similar for those on and off acid-suppressive therapy, but those on PPI/H2RA report more nausea and belching. No difference in acid-suppressive therapy use was observed between FD patients and those with organic findings at endoscopy.

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

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

It is well established that the gut microbiota plays an important role in host health and is perturbed by several factors including antibiotics and diseases like coronavirus disease 2019 (COVID-19). The microbiome contributes to the pathogenesis of ulcerative colitis (UC). Some vitamins have been shown to beneficially modulate the gut microbiome by increasing the abundance of presumed commensals. Also, probiotics could shape the intestinal microbiota leading to potential control of multiple bowel diseases and promotion of overall wellness.

Aims & Methods

In 6-month time (June 2021 to December 2021) 49 ulcerative colitis (UC) outpatients from Riga East Clinical University Hospital were included in a Cross-sectional study. All patients were divided into groups according to medically proven data about COVID-19 status (COVID-19pos vs. COVID-19neg) within the last 6 months. Information about vitamin, probiotic, and antibiotic intake, as well as fecal samples was collected. For taxonomical classifying of the gut microbiome metagenome data, MetaPhlAn v.2.6.0 tool was used. In further analysis gut microbiome (mostly bacteria phyla) and related data were analyzed with SPSS 20.0.

Results

Out of 49 patients, 31(63%) were male and 18(37%) were female, mean age was Md=38[IQR:34-51]. Fourteen patients (28.6%) have been COVID-19pos, 35(71.4%) COVID-19neg. Patients who were not using antibiotics in the last month had more Firmicutes Md= 64 [IQR:52.3-69.4] than users Md=31 [IQR:25.5-39.8], p=0.008. Only 9 patients (18.4%) consumed probiotics within the last month and 40 (81.6%) did not. Evaluating differences in bacteria composition in phylum level in-between probiotic users and non-users there were found no statistically significant difference. Most common used vitamins were vitamin D 18(64.3%), from those 15(42.9%) were COVID-19neg, 3(21.4%) COVID-19pos; vitamin C 7(32.8%), from those 4(11.4%) were COVID-19neg, 3(21.4%) COVID-19pos, p>0.5. Evaluating vitamin D and C users and non-users and bacteria type there were found no statistically significant differences.

Conclusion

Patients who were not using antibiotics in the last month had more Firmicutes than users. There were no statistically significant differences between probiotic users and non-users, nor between vitamin users and non-users.

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

New biologics such as vedolizumab (VDZ) and ustekinumab (UST) have expanded the therapeutic armamentarium for inflammatory bowel diseases (IBD) over the past decade. Head-to-head trials comparing safety to tumor necrosis factor alpha inhibitors (anti-TNF) are limited. Data on safety of biologic sequencing remains scarce.

Aims & Methods

Aim: To assess the impact of different biologics and previous treatments on the incidence of severe adverse events (SAE) in a real-world tertiary IBD patient cohort.
Methods: A retrospective monocentric study was performed at the Ghent University Hospital. Patients starting anti-TNF, VDZ or UST from January 2018 to June 2021 with follow-up until December 2021 were included. SAE were defined as intestinal resection (IR), IBD-inflammation related hospitalization (IBD-hosp), IBD-treatment related hospitalization (e.g. infections) (treat-hosp), malignancy and death. Cox regression analysis was used to explore risk factors (RF) of SAE.

Results

In total 267 patients were included: 84 on VDZ, 69 UST, 60 infliximab (IFX) and 54 adalimumab (ADM). At baseline a significant difference was found between biologic groups for age (younger in IFX and ADM - P=0.001), IBD type (Crohn’s disease (CD): VDZ 51.2%, UST 73.9%, IFX 70%, ADM 77.8% - P=0.003), CRP (in mg/L, med, IQR - VDZ: 5[1.6-12.4], UST: 8.5[2.8-19.3], IFX: 13 [1.87-31.8], ADM:3.2[1-8.1] - P<0.001) and calprotectin (in µg/g, med, IQR) (VDZ: 579 [175- 1801], UST: 707 [244-2889], IFX: 652 [65-2449], ADM 200 [43.7-789] - P=0.021)). Perianal CD rate was higher in anti-TNF and UST patients (P=0.003) and prior disease duration differed significantly (VDZ: 9years, UST10y, IFX 2y,ADM 3.5y - P<0.001)). Concomitant immunomodulator (IMM) use was higher in the IFX group (81.7% vs 25% for all other groups P<0.001)) and corticosteroid (CS) use differed among treatment groups (VDZ 78.6%, UST 68.1%, IFX 70%, ADM 55.6% (P=0.041)). Number of prior biologics was higher in the UST group (P<0.001).
No significant difference in SAE rate could be found between different biologics (UST 37.7%, IFX 33.3%, VDZ 23.8%, ADM 22.2% - P=0.148). Cox regression revealed age ≥60years (aHR 2.00, 95%CI 1.11-3.60, P=0.020) and higher number of previous biologics (aHR 1.29, 95%CI 1.03-1.60, P=0.024) as independent RF for SAE. Considering SAEs types, IR rate was not significantly different between biologic groups (VDZ 4.8%, UST 15.9%, IFX 8.3%, ADM 5.6% - P=0.096). Cox regression revealed previous IMM use as an independent RF for IR (aHR 4.26, 95%CI 1.62-11.19, P=0.003). No significant difference was found between biologics considering IBD-hosp (VDZ 15.5%, UST 30.4%, IFX 21.7%, ADM 14.8% – P=0.087). Higher number of previous biologics was an independent RF for IBD-hosp (aHR 1.32, 95%CI 1.02-1.71, P=0.036). Treat-hosp rate was not significantly different between biologic groups (VDZ 7.1%, UST 10.1%, IFX 6.7%, ADM 5.6% – P=0.811). Age ≥60years was found to be an independent RF of treat-hosp (aHR 4.93, 95%CI 1.91-12.76, P=0.001). Six patients developed malignancy (3 VDZ: colorectal carcinoma, melanoma, low grade appendix neoplasia; 2 IFX: cervix CIN3, gastric adenocarcinoma; 1 ADM: basal cell carcinoma). One patient died due to progressive melanoma while on VDZ.

Conclusion

In this tertiary real-world IBD patient cohort, no influence of type of biologic on the SAE rate could be found. Elderly age (≥60 years) and higher number of previous biologics were an independent RF for SAEs.