Introduction

Crohn’s disease (CD) is a chronic inflammatory condition that leads to cumulative structural bowel damage. The Lémann Index is a validated tool that can be a useful for monitoring the progression of the disease and evaluating the effectiveness of different therapies. Recent data have shown a range of biomarkers and endoscopic findings preceding the diagnosis of CD.

Aims & Methods

Our aim was to describe the most frequent cross-sectional findings in asymptomatic patients with an incidental diagnosis of CD and to evaluate the progression of bowel damage from a preclinical stage until the symptomatic onset of the disease. Patients with an incidental diagnosis of CD during the colorectal cancer screening programme were included. Only patients with available MRI enterography were included. They were compared 1:1 to controls matched by disease extent from an inception cohort of patients with CD diagnosed after symptomatic onset of the disease. All cross-sectional examinations were centrally-read by one experienced radiologist, performing a descriptive analysis of the main radiological findings and calculation of Lémann score on both cohorts. Descriptive statistics were used along with comparisons with chi-square tests and Mann-Whitney analysis.

Results

A total of 38 patients were included: 19 cases with preclinical CD and 19 matched-controls (age 55 years (IQR, 54-62) vs 49 years (IQR, 45-58); 53% vs 42% male; 74% vs 53% non-smokers, respectively). CD location was 53% L1, 21% L2 and 26% L3; and CD behaviour was B1 in 74% vs 79%; B2 in 26% vs 16%; and none vs 5%, among cases and controls, respectively.
The most frequent transmural findings on MRI were contrast enhancement and wall thickening (79% respectively), followed by oedema (42%), while among extraintestinal findings they were lymphadenopathy (68%) and increased vascularity (42%). Among patients with strictures, controls showed a higher rate of preestenotic dilation (100% vs 0%, p=0.01).
Bowel damage assessment revealed no statistically significant differences in the Lémann index between preclinical CD and controls (p=0.95). However, we observed that cases had statistically significant higher scores in the colonic/rectum score (p=0.014). We found no differences in the Lémann index between preclinical CD patients who subsenquently developed symptoms (median LI 1.0 [IQR, 0.3-2.0]) and those who did not (1.1 [IQR, 0.68-2.65], respectively, p=0.71) or with controls (1.3 [IQR, 0.0-3.1], respectively, p=0.96).

Conclusion

Patients with preclinical CD demonstrate similar findings on MRI enterography and they have the same degree of bowel damage as new-onset symptomatic CD. Close monitoring should be recommended based on these findings.

Introduction

Helicobacter pylori (H. pylori) infection has a high prevalence (44.8%) in China and is an important risk factor of gastrointestinal diseases including gastric cancer. Bismuth quadruple therapy (BQT; bismuth + acid suppressant + 2 antibiotics [ABs]) is the currently recommended first-line regimen for H. pylori in China. Increasing AB resistance poses a vital challenge and remarkably reduces the eradication rate (ER) from 95% to 80% globally and 89% to 78% in China. Real-world ER analysis assessed only quadruple therapy in a few single centers and did not focus on different antibiotic combinations and other different regimens.

Aims & Methods

This study was designed to evaluate the diagnosis and treatment pattern of H. pylori infection and the effectiveness of eradication therapy in real-world settings in China. In this retrospective, multicenter study (NCT05073367), de-identified patient data were extracted from the electronic medical records database of 3 hospitals between January 1, 2019, and March 31, 2021. Patients aged ≥18 years with a record of H. pylori infection diagnosis were included. Here we presented the eradication rate of different treatment regimens and the eradication rate of different years with different treatment regimens.

Results

A total of 1426 patients received ET with efficacy evaluation duration＞4 weeks after the eradication therapy and the total eradication rate was 72.09% (n=1028). Most patients (80.36%; n=1146) received standard BQT with an ER of 76.70% (n=879). 158 patients (11.08%) received dual therapy (ER=56.96%; n=90) and 122 patients (8.56%) received triple therapy (ER=48.36%; n=59). Compared with triple and dual therapies, BQT was the predominant regimen in all the years with an ER of 77.86%, 67.64%, and 82.78% in 2019, 2020, and 2021, respectively. The ER of dual therapy was 50% in 2020 and 61.22% in 2021. The triple therapy ER showed a decreasing trend with 78.57% (n=11), 46.25% (n=37), 39.29% (n=11) from 2019 to 2021. Among the BQT regimens, amoxicillin plus furazolidone based regimens showed a higher ER (87.44%; n=181), while the ER of amoxicillin plus levofloxacin, amoxicillin plus clarithromycin based BQT was 77.94% (n=159) and 76.07% (n=391), respectively. Amoxicillin plus furazolidone based BQT showed a higher ER of 87.30%, 83.02%, and 90.11% in 2019, 2020, and 2021 respectively (Table 1).
Table 1. Eradication rate of H. pylori positive patients based on the type of eradication therapy

Conclusion

BQT-based regimens were predominantly prescribed for H. pylori management and the current H. pylori treatment regimens have a suboptimal eradication rate in the real-world settings.

Disclosure

The study was funded by Takeda China. Wensheng Pan, Yan Zhao, and Hongwei Xu have no conflicts of interest. Pengfei Li, Fang Zhou, and Li Xie are employees of Takeda, and they hold Takeda stock options. Medical writing for the development of this abstract was provided by Swathirajan CR, PhD, and Kusuma Kumari G, PhD, of Indegene Private Limited, and funded by Takeda China. Authors retained full control of the abstract content.

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

Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms characterised by a highly heterogeneous biological behaviour. Currently available preoperative prognostic factors for Non-functioning Pancreatic Neuroendocrine Tumors (NF-PanNETs) still struggle to properly predict tumor aggressiveness, making an adequate management of these lesions hard to be achieved. Aims of this study were: i) to evaluate treatment appropriateness in patients submitted to surgery for NF-PanNETs, and ii) to investigate preoperative features predicting under- or over-treatment in these patients.

Aims & Methods

Patients who underwent curative surgery (R0-R1) for NF-PanNETs at San Raffaele Hospital (Milan, Italy) between November 2002 and March 2022, were retrospectively analysed. Treatment appropriateness was categorized as appropriate treatment, overtreatment, and undertreatment. The presence of features of aggressiveness at final histology and the occurrence of disease relapse within one year from surgery were considered to define treatment appropriateness.

Results

Conclusion

Overtreatment occurs in almost one-third of patients undergoing surgery for NF-PanNETs. However, over the last decade, the percentage of appropriately treated patients has been steadily increasing. A more careful assessment of lesions located in the pancreatic body-tail and/or with a radiological diameter <25.5mm should be performed in order to increase the adequacy of treatment selection.

Introduction

Thermal ablative methods (such as argon plasma coagulation (APC) and soft tip snare coagulation (STSC) are commonly used to treat polyp margins.

Aims & Methods

We aim to appraise the current literature and compare clinical outcomes between patients with treated (with APC vs STSC) and non-treated EMR margins.
We searched major databases from inception until November 2023 for RCTs comparing EMR of large non-pedunculated colorectal polyps with and without treated margins. Pooled data was analyzed for the primary outcome of recurrence at first screening colonoscopy, as well as adverse events. Analysis was performed using a random effects model and data was reported using 95% confidence intervals (CI).

Results

A total of five RCTs were found which included 1020 polyps (577 in treatment and 443 in control groups). Three studies included treatment with STSC and three studies used APC as the modality for margin ablation. Of included patients, 53% were female and average age was similar between treatment and control groups (65.9 vs 66.1 years). Overall, 71% of lesions were proximal to the splenic flexure. Mean follow up to first colonoscopy and average polyp size were comparable (6.3 vs 6.2 months; 28.2 mm vs 28.0 mm, respectively). Pooled analysis showed that margin ablation was associated with significantly lower rates of recurrence (OR = 0.267, 95% CI 0.18 - 0.4, P< 0.001) with low heterogeneity between studies (I²=0%, P = 0.47). Pooled analysis showed no significant difference between STSC and APC in terms of recurrence (OR = 0.6, 95% CI 0.27 - 1.7, I²=0%, P=0.3) or adverse events (OR = 0.67, 95% CI 0.3 - 1.6, I² 13%, P = 0.46).

Conclusion

Our study shows that ablation of EMR margins is very effective at preventing recurrence at first surveillance colonoscopy. We found no difference between STSC or APC in terms of polyp recurrence or adverse outcomes.

Introduction

Pancreatic cancer (PC) is the fourth-leading cause of cancer-related death, with over 80% of patients having unresectable disease upon diagnosis. Despite opioid treatment, more than 70% of this population is experiencing chronic pain during the disease, along with a plethora of side effects. In the past decades, interventional radiological procedures have gained a significant role in pain management.

Aims & Methods

Our study aims to identify the most effective approach for managing pain in individuals with unresectable pancreatic cancer. We registered the study on PROSPERO (CRD42023477094) and systematically searched five major scientific databases on the 29th of October, 2023. Only randomised controlled trials (RCTs) reporting on adult patients diagnosed with unresectable PC and cancer-related pain undergoing medical or interventional treatment were considered eligible. The main intervention groups were endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN), percutaneous celiac plexus neurolysis (P-CPN), high-intensity focused ultrasound (HIFU), and pharmacological therapy (opioids). Our outcomes of interest were pain, survival, and adverse events. Pooled means and proportions were calculated with 95% confidence intervals (CIs), and a random-effects model was applied.

Results

After title-abstract and full-text article selection, 1644 patients of 21 RCTs were found eligible. The pain was assessed using the 11-point Visual Analogue Scale from randomisation at 4, 8 and 12 weeks to determine its dynamic over time. Pain values at baseline were 6.09 (CI: 4.24-7.94) for EUS-CPN, 6.67 (CI: 5.20-8.14) for P-CPN, 6.57 (CI: 4.98-8.15) for HIFU, and 6.47 (CI: 5.02-7.93) for opioids. At one month, the overall pain score was 1.53 (CI: 0.23- 2.82) for EUS-CPN, 2.21 (CI: 1.43-2.91) for P-CPN and 2.68 (CI: 1.94-3.42) for opioids. At two and three months after randomisation, there was a slow but continuous increase in pain scores for all treatment groups. The median survival time in days was 126.22 (CI: 87.21-165.31) for pharmacological treatment and 86.71 (CI: 62.45-136.88) for P-CPN. Patients receiving only opioids developed more adverse events compared to P-CPN, the most common being nausea, vomiting, and constipation. EUS-CPN had the lowest rate of adverse events.

Conclusion

Our study shows that minimal-invasive pain treatments provide pain control with fewer adverse events associated, with EUS-CPN having the most promising results. However, further RCTs with higher sample sizes are needed to confirm our findings.

References

1. Wong et al., Effect of Neurolytic Celiac Plexus Block on Pain Relief, Quality of Life, and Survival in Patients with Unresectable Pancreatic Cancer - A Randomized Controlled Trial JAMA. 2004; 291:1092-1099
2. Dong et al., Neurolytic Splanchnic Nerve Block and Pain Relief, Survival, and Quality of Life in Unresectable Pancreatic Cancer: A Randomized Controlled Trial, Anesthesiology 2021; 135:686–98
3. Gao et al., A randomized clinical trial of nerve block to manage end-stage pancreatic cancerous pain, Tumor Biol. (2014) 35:2297–2301
4. Kanno et al., Efficacy of EUS-guided celiac plexus neurolysis compared with medication alone for unresectable pancreatic cancer in the oxycodone/fentanyl era: a prospective randomized control study, Gastrointest Endosc 2020;92:120-30
5. Zhang et al., Effect of Neurolytic Celiac Plexus Block Guided by Computerized Tomography on Pancreatic Cancer Pain, Dig Dis Sci (2008) 53:856–860
6. Lv et al., High-intensity focused ultrasound therapy in combination with gemcitabine for unresectable pancreatic carcinoma, Therapeutics and Clinical Risk Management 2016:12 687–691
7. Li et al., Retrospective analysis of high intensity focused ultrasound combined with S-1 in the treatment of metastatic pancreatic cancer after failure of gemcitabine, Am J Cancer Res 2016;6(1):84-90

Introduction

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that often affects multiple organs. Glucocorticoids (GCs) are often used first-line for the treatment of IgG4-RD.¹ Despite their therapeutic benefits, long-term GC use is known to be associated with toxicities that can affect several organ systems.¹ While the association between GC exposure and toxicities has been well characterized in other conditions, little is known about the real-world use of GCs and the associated clinical burden in the context of IgG4-RD.

Aims & Methods

Commercially insured adults (age ≥18 years) diagnosed with IgG4-RD were identified in the IQVIA PharMetrics® Plus database (01/01/2011-06/30/2022) using a validated algorithm. This algorithm considered IgG4-RD-related diagnoses, prescription medication fills, and medical procedures.² The index date was defined as the first observed IgG4-RD-related diagnosis code, and the baseline and follow-up periods were defined as the 12 months before and after the index date, respectively. GC use during the follow-up period was calculated as the total cumulative prednisone equivalent dose divided by 365 days. Patients were classified into two mutually exclusive cohorts based on GC use. The low GC use cohort comprised patients with a mean GC dose of <5 mg/day, including patients with no GC use; the high GC use cohort comprised those with a mean GC dose of ≥5 mg/day. Incident GC toxicities were defined as toxicities with ≥1 diagnosis during the follow-up period and no diagnosis during the baseline period. Demographic characteristics were reported as of the index date; GC use and incident toxicities were reported during the follow-up period. Descriptive comparisons of incident toxicities between cohorts were analyzed using Chi-square tests.

Results

A total of 295 patients with IgG4-RD were identified, with 150 (50.8%) included in the low GC use cohort (mean age 48.9 years, 55.3% female) and 145 (49.2%) in the high GC use cohort (mean age 50.8 years, 45.5% female). In the first year after diagnosis, most patients (84.1%) received ≥1 GC fill, with a mean of 4.1 fills, corresponding to 3.9 months of treatment. Patients in the low GC use cohort received a mean of 1.8 fills, corresponding to 1.4 months of treatment or a mean dose of 1.4 mg/day over the 12-month follow-up period. Patients in the high GC use cohort received 6.4 fills, corresponding to 6.5 months of treatments or a mean dose of 12.0 mg/day over the follow-up period. Higher GC use was associated with higher rates of incident GC toxicities, such that patients in the high GC use cohort had a greater mean number of GC toxicities (1.8 vs. 1.2; p<0.01) and were more likely to have ≥3 toxicities (29.0% vs. 13.3%; p<0.01) than the low GC use cohort. In particular, cardiovascular (29.0% vs. 18.7%; p=0.04), gastrointestinal (29.7% vs. 16.0%; p<0.01), and infectious (31.0% vs. 17.3%; p<0.01) toxicities were more commonly observed among patients with high GC use than low GC use.

Conclusion

In the first year after diagnosis, patients with IgG4-RD experienced a substantial GC burden, as evidenced by nearly half of them exposed to high GC use. Higher GC use was associated with an increased incidence of GC toxicities across multiple organ systems. These findings suggest an unmet need for safe and effective treatments to mitigate prolonged exposure to GCs and improve patient outcomes, particularly in the absence of targeted FDA-approved therapies for IgG4-RD.

References

1. Yasir M, et al. 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK531462/.
2. Wallace ZS, et al. ACR Open Rheumatol. 2022;4(4):371–7.

Disclosure

Z.S. Wallace, E. Serra, A. Guérin, and V.K. Singh have received consulting fees from Amgen Inc.
J. Park, K.R. Patterson, H. Patel are employees of Amgen Inc. and hold stock.

Study and abstract were funded by Amgen Inc.