Introduction

Hepatocellular carcinoma (HCC) is a global problem being fourth in terms of cancer-related deaths¹. Contrast-enhanced ultrasound (CEUS) is used as an add-on test to confirm focal liver lesions suspected as HCC at prior diagnostic tests such as ultrasound or alpha-foetoprotein, or both^2,3. According to guidelines^4,5,6, a single contrast-enhanced imaging techniques, with either computed tomography (CT) or magnetic resonance imaging (MRI) showing the typical hallmarks is sufficient to diagnose HCC in cirrhotic patients. However, a significant number of HCC show atypical imaging features, and therefore, are missed at imaging.
The advantages of CEUS over CT and MRI is the use of contrast agents not containing iodine and that are not nephrotoxic, and quick image acquisition. Despite the advantages, the use of CEUS in the diagnostic algorithm for HCC remains controversial, with disagreement on relevant guidelines.

Aims & Methods

The aim was to assess the diagnostic accuracy of CEUS for the diagnosis of HCC of any size and at any stage in adults with chronic liver disease, in a surveillance programme or in a clinical setting and to assess the diagnostic accuracy of CEUS for the diagnosis of resectable HCC in people with chronic liver disease and identify potential sources of heterogeneity in the results.
We included studies assessing the diagnostic accuracy of CEUS for the diagnosis of HCC in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver, and histology of resected or biopsied focal liver lesion with at least a six-month follow-up.
Standard Cochrane methods ⁷ were used to screen studies, extract data, and assess the risk of bias and applicability concerns, using the QUADAS-2 checklist⁸. We used the bivariate model and provided estimates of summary sensitivity and specificity. We assessed the certainty of the evidence using GRADE^9,10. We presented uncertainty-of-the-accuracy estimates using 95% confidence intervals (CIs).

Results

We included 23 studies with 6546 participants. Studies were published between 2001 and 2021. We judged all 23 studies at high-risk of bias in at least one domain, and 13/23 studies at high concern for applicability. Most studies used different reference standards to exclude the presence of the target condition. The time interval between the index test and the reference standard was rarely defined. We also had major concerns on their applicability due to the participant characteristics.
CEUS for HCC of any size and stage: sensitivity 77.8% (95% CI 69.4% to 84.4%) and specificity 93.8% (95% CI 89.1% to 96.6%) (23 studies, 6546 participants; very low-certainty evidence).
CEUS for resectable HCC: sensitivity 77.5% (95% CI 62.9% to 87.6%) and specificity 92.7% (95% CI 86.8% to 96.1%) (13 studies, 1257 participants; low-certainty evidence).
The observed heterogeneity in the results remains unexplained.

Conclusion

Using CEUS, as an add-on test following abdominal ultrasound, to diagnose HCC of any size and stage, 22% of people with the tumor would be missed, and 6% of people without would unnecessarily undergo further testing or inappropriate treatment. As to resectable HCC, we found that 23% of people with resectable tumor would incorrectly be unresected, while 8% of people without HCC would undergo further inappropriate testing or treatment. The uncertainty resulting from the high risk of bias of the included studies, heterogeneity, and imprecision of the results and concerns on their applicability limit our ability to draw confident conclusions.

References

1) Forner A et al. Hepatocellular carcinoma. Lancet 2018;391(10127):1301-14.
2) Niu Y, et al. Contrast-enhanced ultrasonography for the diagnosis of small hepatocellular carcinoma: a metaanalysis and meta-regression analysis. Tumour Biology
2013;34(6):3667-74.
3) VogelA, et al. Hepatocellular carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of Oncology2019;30(5):871-3.
4) Galle PR, et al. EASL clinical practice guidelines: management of hepatocellular carcinoma. Journal of Hepatology 2018;69(1):182-236.
5) Omata M, et al.Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatology International 2017;11:317-70
6) HeimbachJK,, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358-80.
7) Macaskill P, et al. Chapter 10: Understanding meta-analysis Draft version (13 May 2022) for inclusion in: Deeks JJ, Bossuyt PM, Leeflang MM, TakwoingiY, editor(s). Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy Version 2. London: Cochrane.
8) Whiting PF, Ret al. QUADAS-2 Group. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Annals of Internal Medicine 2011;155(8):529-36.
9) McMaster University (developed by Evidence Prime) GRADEpro GDT. Version accessed 26 January 2022. Hamilton (ON): McMaster University (developed by Evidence Prime). Available at gradepro.org.





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Disclosure

nothing to disclose

Introduction

Patients with type 2 diabetes are prone to the development of dysbiosis, which can manifest as intestinal bacterial overgrowth (SIBO). This may explain the pathomechanism of abdominal symptoms that sometimes affect this group of patients. Disturbances in the composition and quantity of intestinal microbiota translate to impaired production of short-chain fatty acids (SCFA) in the intestinal mucosa. To increase the concentration of butyrate in the lumen of the intestine, oral microencapsulated sodium butyrate supplementation can be proposed. Given the limited research conducted on the topic of the effects of sodium butyrate supplementation in alleviating abdominal symptoms in patients with type 2 diabetes, it became the topic of our interest.

Aims & Methods

The aim of the study was to evaluate the effectiveness of oral sodium butyrate supplementation in the population of patients with type 2 diabetes in alleviating abdominal symptoms and to estimate the incidence of small intestinal bacterial overgrowth in this group. In addition, the impact of the intervention on the carbohydrate metabolism was assessed.A prospective, single-centre, randomized, placebo-controlled study was conducted between October 2022 and April 2023.
52 patients with type 2 diabetes and gastrointestinal symptoms were randomly assigned to one of 2 groups - a group receiving microencapsulated sodium butyrate (Intesta Max) at a dose of 1.5 g/day and a group receiving placebo. As 8 patients (15.3%) were lost to follow-up, for the preliminary analysis 44 patients were included. The study lasted for 6 weeks. Before and after the intervention the presence of abdominal pain, diarrhoea, constipation and flatulence was assessed, laboratory tests and hydrogen breath tests were performed, the HOMA index and body mass index were calculated.

Results

At baseline SIBO was diagnosed in 73.1% of patients in the experimental group and 58.8% of patients in the control group. After 6 weeks of the intervention there was a significant drop in SIBO occurrence in sodium butyrate group – 22.2% (p=0.001). The incidence of SIBO in the control group did not change – 64.7% (p=0.21).All patients included in the study declared abdominal pain before the intervention. After 6 weeks the pain was reported by 42.3% of the patients receiving the sodium butyrate vs. 88.4% of the patients receiving placebo (p=0.002). After the intervention there was a significant difference between the groups regarding diarrhea – 18.5% and 58.8% (p=0.006) in sodium butyrate and placebo groups respectively. A decrease in the incidence of bloating in the sodium butyrate group was observed - 100% before vs. 29,6% after the intervention (p<0.00001). The study also showed a decrease in BMI level, the HOMA index and glycated hemoglobin level after consumption of the sodium butyrate vs. placebo for 6 weeks. These results need confirmation in a larger group.

Conclusion

To our knowledge this is the first study reporting the effectiveness of oral butyric sodium supplementation in relieving abdominal symptoms (abdominal pain, diarrhea, flatulence) in patients with type 2 diabetes. Furthermore, an improvement in carbohydrate metabolism parameters was noted and body weight decrease was observed after the intervention.

Disclosure

Sodium butyrate (Intesta Max) we received from the company that produces it.

Introduction

Bowel urgency is increasingly recognized as a common and impactful symptom in patients with Ulcerative Colitis (UC)¹. However, there are limited data exploring the relationship of bowel urgency with work productivity. We examined the relative association of bowel urgency clinically meaningful improvement (CMI) and bowel urgency remission with Work Productivity and Activity Impairment (WPAI) scores in the presence of rectal bleeding (RB) remission and stool frequency (SF) remission as potential confounding variables using data from LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) phase 3 trials.

Aims & Methods

Bowel urgency severity was assessed using the Urgency Numeric Rating Scale (UNRS; 0=no urgency to 10=worst possible urgency). Bowel urgency CMI is a ≥3-point decrease and bowel urgency remission is a UNRS score of 0 or 1². WPAI scores (absenteeism, presenteeism, and work productivity loss in employed patients, and activity impairment in all patients) were measured using a 6-item questionnaire; higher scores indicate greater impairment and less productivity. Mediation analyses were performed to separately examine the relative association between the direct effect of bowel urgency CMI and bowel urgency remission (predictor) and WPAI scores while adjusting for the potential confounding effects of RB remission and SF remission (mediator). Analyses were treatment agnostic and combined patients from mirikizumab and placebo groups from LUCENT-1 (N=1162) and LUCENT-2 (N=544) trials.

Results

At week (W)12 and W52, the direct effect of bowel urgency remission accounted for 43%–49% and 27%–57% of the improvement in all WPAI domain scores except absenteeism, respectively. The association values greater than 100% at W12 and W52 (153% and 148%, respectively) reflect the critical importance of SF remission in the improvement of absenteeism score. Bowel urgency CMI resulted in the largest proportion of improvement in WPAI domain scores (except absenteeism) at W12 (71%–74%) and W52 (66%–78%). Bowel urgency CMI accounted for 68% and 239% of the improvement in absenteeism scores at W12 and W52, respectively. At W52, 750% of the effect was mediated by RB remission.

Conclusion

Improvement in work productivity and regular activities were primarily ascribed to bowel urgency remission or bowel urgency CMI relative to RB remission and SF remission in patients with moderately-to-severely active UC. These findings suggest that bowel urgency is a critical and independent symptom that considerably impacts patients’ productivity.

References

1. Dubinsky MC, et al. Crohn's & Colitis 360. Volume 4, Issue 3, July 2022;7(4):3.
2. Dubinsky MC, et al. J Patient Rep Outcomes. 2022;6(1):114.

Disclosure

Bruce Sands: Consulting: Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Boehringer-Ingelheim, Boston Pharmaceuticals, Calibr, Celltrion Healthcare, ClostraBio, Entera, Evommune, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Inotrem, Innovation Therapeutics, Ironwood Pharmaceuticals, Kaleido, Kallyope, Lilly, Miro Bio, Morphic Therapeutics, MRM Health, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Q32 Bio, Surrozen, Teva, TLL Pharmaceutical, USWM Enterprises, VielaBio; consulting, speaking, research funding: Bristol Myers Squibb; consulting, speaking, grant/research support: Janssen; consulting, speaking: Abivax, Pfizer, Takeda
Brian Feagan: Consulting: AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc., Arena Pharma, Avir, Azora Therapeutics, BioJamp, Biora Therapeutics, Boehringer-Ingelheim, Boston Pharma, Boxer, Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Everest Clinical Research Corp., Lilly, Equillium, Ermium, Ferring, First Wave, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Glenmark, Gossamer Pharma, GSK, Hoffmann-LaRoche, Hot Spot Therapeutics, Index Pharma, Imhotex, ImmunExt, Immunic Therapeutics, Intact Therapeutics, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, LifeSci Capital, Lument AB, Millennium, MiroBio, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Otsuka, Pandion Therapeutics, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, RedHill, Biopharma, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Theravance, Tigenix, Tillotts, UCB Pharma, VHSquared Ltd., Viatris, Ysios, Ysopia, Zealand Pharma; speakers bureau: AbbVie, Janssen, Takeda. Scientific advisory board member: AbbVie, Amgen, Boehringer-Ingelheim, Celgene/BMS Genentech/Roche, Janssen, Novartis, Origo BioPharma, Pfizer, Prometheus, Takeda,Tillotts Pharma, Teva, Progenity, Index, Ecor1Capital, Morphic, GSK; stock shareholder: Gossamer Pharma.
Employment: Western University, Alimentiv Inc.
Stefan Schreiber: Consulting and personal fees: AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Galapagos/Gilead, HIKMA, IMAB, Janssen, Lilly, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Takeda, and Theravance.
Vipul Jairath: Consulting/advisory board fees: AbbVie, Alimentiv Inc., Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, BMS, Celltrion, Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso pharmaceuticals, Takeda, Teva, Topivert, Ventyx, Vividion. Speaker’s fees: Abbvie, Ferring, BMS, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi.
Alessandro Armuzzi: Consulting/advisory board fees: AbbVie, Allergan, Amgen, Arena, Biogen, Boehringer-Ingelheim, BMS, Celgene, Celltrion, Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda.
Speaker’s fees: AbbVie, Amgen, Arena, Biogen, BMS, Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Tigenix.
Research grants: MSD, Takeda, Pfizer, Biogen.
Theresa Hunter Gibble: Employment and stockholder: Eli Lilly and Company
Anthony Keohane: Employment and stockholder: Eli Lilly and Company
William J Eastman: Employment and stockholder: Eli Lilly and Company
Kristina A Traxler: Employment and stockholder: Eli Lilly and Company

Introduction

The implementation of colorectal cancer screening programmes has been associated with an increase in the incidence of malignant polyps removed endoscopically. In those without endoscopic cure criteria, surgery can be performed to improve oncological outcomes.

Aims & Methods

Evaluate factors associated with the presence of residual malignant disease in the surgical specimen after endoscopic removal of a malignant polyp without endoscopic cure.
Retrospective, cohort study including patients with a malignant polyp endoscopically removed without endoscopic cure, who underwent surgery. The absence of endoscopic cure was defined as positive vertical resection margins (< 1 mm), poorly differentiated grade, depth of submucosal invasion > 1 mm, presence of lymphatic or vascular invasion, or presence of tumour budding. Patients with a synchronous neoplastic lesion and those with a malignant polyp without complete endoscopic removal were excluded.

Results

Included 74 consecutive patients submitted to surgery after the endoscopic removal of a malignant polyp without endoscopic cure. Most patients were male (62.2%), with a mean age of 64 ± 10 years. Regarding the endoscopic mucosal resection (EMR), 45 polyps were removed in one fragment (60.8%) and the other 29 were submitted to piecemeal EMR (39.2%). In 15 cases, snare tip spray coagulation (STSC) was performed at the margins of mucosal defects after EMR, 6 in normal-appearing margins (8.1%) and 9 in margins suspected of residual adenomatous tissue (12.2%). Considering the post-operative outcomes, 7 patients required surgical re-intervention (9.5%), 1 was admitted in the intensive care unit (1.4%), 1 patient died (1.4%), and 2 patients required re-hospitalization in the following 6 months (2.7%).
The presence of residual malignant disease in the surgical specimen occurred in 9 patients (12.2%), 7 had intramural disease (9.5%) and 2 had nodal metastasis (2.7%). Patients with polyps with a flat component were 5 times more likely to have residual disease in the surgical specimen (p=0.043). The polyp size and its location in the right colon were not associated with the presence of residual disease in the surgical specimen (p=0.140 and p=0.654, respectively). Patients with polyps submitted to piecemeal EMR were 7 times more likely to have residual disease in the surgical specimen (p=0.024), with 2 patients with residual disease after EMR in one fragment (4.4%) and 7 patients with residual disease from the piecemeal EMR group (24.1%). Those in which STSC was performed were also more likely to have residual disease in the surgical specimen (p<0.001). No statistically significant differences were found between the presence of positive margins, lymphatic or vascular invasion or well or moderately differentiated histologic grade, and the presence of residual disease in the surgical specimen (p=1.000, p=0.675 and p=0.686, respectively). Tumour budding was described in 3 patients, none of which had residual disease in the surgical specimen.

Conclusion

A minority of patients had residual malignant disease in the surgical specimen, with a higher risk for those with polyps with a flat component or that were submitted to piecemeal EMR. In fact, with piecemeal EMR almost one quarter of patients had residual disease e less than 5% of those with EMR in one fragment had residual disease in the surgical specimen, highlighting the need for a careful evaluation of the polyp before endoscopic removal and the importance of removal in one fragment, in case of suspected submucosal invasion.