Introduction

Anaemia is common and in some cases an indication for an urgent endoscopy via two week wait (2WW) pathway. This pathway allows patients with alarming symptoms to see a specialist within two weeks to exclude cancer. In this retrospective study, we assessed the clinical outcomes of such referrals, describing the types of cancer identified after full investigations in our centre.

Aims & Methods

Data was collected between December 2021 and December 2022 using Endoscopy UNISOFT system for all endoscopy procedures prompted by anaemia at Milton Keynes University Hospital, United Kingdom. Basic demographics, faecal immunochemical test (FIT) and 2WW referrals from both upper gastrointestinal (UGI) or colorectal pathway were recorded. Radiological images and multi-disciplinary team outcomes were reviewed.

Results

Total number of patients referred to our endoscopy unit was 389, 70% were referred via colorectal team while 30% were referred via UGI pathway. Age of patients was distributed between 19 to 98 years old with majority aged between 60 to 88 years old. 227 patients had both gastroscopy (OGD) + colonoscopy (COL), 76 had OGD+CT scan, 9 patients had OGD+COL+CT and 5 patients had COL+CT. The other patients had CT only, OGD only, or COL only, depending on fitness.
Data revealed that 33 (8.5%) patients referred with anaemia had cancer. 21 patients had colorectal cancer while 8 patients had upper GI cancer. Non-GI cancers were found in four patients, 2 of them lung cancer, 1 renal cancer and 1 tonsillar cancer. There were 187 patients (48%) that had UGI non-cancer pathology e.g. gastritis, duodenitis, peptic ulcer disease, oesophageal varices and coeliac disease. The remaining causes of anaemia are found in Table 1.

Table 1: Causes of Anaemia

Conclusion

The percentage of cancer in our population with anaemia was 8.5%. The main gastrointestinal cancer was colon cancer (5.4%), followed by upper gastrointestinal cancer (2.05%) and non-GI cancer was (1.02%) only. According to previous data, 8%-10% of cases with anaemia were found to have cancer which is not very different from our audit (1,2). The most common cause of anaemia was UGI non-cancer pathology, however, there was no clear aetiology identified in 23% of our population. Four non-GI cancer were discovered by radiological images/CT scans. Those patients with non-GI cancer were above the age of 60. Although the number is small, radiological imaging remains an important tool to investigate anaemia in elderly people when both OGD and colonoscopy are unremarkable. FIT test revealed a high false positive rate with only 14% with positive FIT test had colorectal cancer.

References

1. Snook, J. et al.(2021) British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults,Gut. 2021 Nov;70(11):2030-2051.

1. James MW, et al.(2005) Risk factors for gastrointestinal malignancy in patients with iron-deficiency anaemia.Eur J Gastroenterol Hepatol 2005;17:1197–203

Clinical Case Summary

A 13-year-old boy presented with abdominal distention, recurrent hypoglycemia, and self-resolving jaundice. Clinical examination revealed growth retardation and hepatosplenomegaly. Blood work revealed anemia, thrombocytopenia, elevated aspartate and alanine transaminase levels, and raised plasma cholesterol and triglycerides. Ultrasound showed an enlarged liver with surface irregularity, splenomegaly, and a dilated portal vein. Etiological work-up for cirrhosis was positive for hepatitis B (HBV) surface antigen (HbsAg) and antibodies for HBV core and envelope antigens (anti Hbc, antiHbe) but an undetectable HBV DNA level. HBV was considered to be an unlikely cause of cirrhosis due to the young age of the patient, hence further metabolic and genetic work-up was done. Tests for Wilson’s and autoimmune liver disease were negative. Liver biopsy revealed a distorted lobular architecture with nodules, thin septae, and portal fibrosis. Hepatocytes showed marked swelling and pyknotic nuclei, and negative HbsAg immunostaining. Molecular analysis revealed a novel mutation in the exon 3 of the PHKG2 gene (c.98G>T, p.Gly33Val). The patient was diagnosed with cirrhosis due to GSD IXc with inactive chronic hepatitis B. His symptoms resolved with an optimized diet of corn starch, high-protein and vitamin supplementation. The importance of liver transplantation was also discussed with the family.

Introduction

Although atezolizumab plus bevacizumab treatment (AB) has been developed as the first immune therapy for unresectable hepatocellular carcinoma (u-HCC) based on the results of the IMbrave 150 trial, there have been few reports of the therapeutic efficacy and safety of AB for u-HCC in real-world clinical practice with a large cohort.

Aims & Methods

This study aimed to elucidate the therapeutic outcome of AB.From 2020 to 2023, 1016 Japanese patients with u-HCC treated with AB in our hospitals were enrolled (median age: 74 years, initial line use: 697, BCLC stage 0 or A:B:C:D=77:408:512:19). Child-Pugh classification and modified albumin-bilirubin (ALBI) grade, in which the middle grade was divided into 2 sub-grades by an ALBI score of -2.27, were used for the assessment of hepatic reserve function. The therapeutic efficacy and safety of AB were evaluated, retrospectively.

Results

The median observation period was 12.5 months (IQR 6.8-21.2). Child-Pugh class A included 920 patients, B included 95, and C included 1, while ALBI grade 1 comprised 360 patients, grade 2 comprised 641 (grade 2a:2b=266:375), and grade 3 comprised 15. The median progression-free survival (mPFS) and overall survival (mOS) in the entire cohort were 7.6 months (95% CI 6.7-8.3) and 22.3 months (95% CI: 19.2-25.5). The mPFS/mOS according to Child-Pugh class (A:B:C) were 7.8/24.5, 5.0/9.4, and 0.4/1.1 months, respectively, while those according to modified ALBI (1:2a:2b:3) were 10.6/31.0, 8.0/22.1, 5.9/14.1, and 5.3/10.5 months, respectively (each P<0.001). According to BCLC stage (0 or A:B:C:D), mPFS/mOS were 14.5/not reached, 9.1/25.1, 6.0/19.1, and 2.4/10.5 months, respectively (each P<0.001). When PFS and OS were compared between initial and later line use groups, significant differences were observed (mPFS/mOS=7.9/24.9 vs. 6.5/18.8 months, respectively, each P<0.05). Adverse events (any grade>10%/grade 3 or more, %) included urine protein (31.7/9.3), fatigue (23.4/2.7), appetite loss (20.2/2.8), hypertension (18.1/5.5), hepatic function abnormality (17.0/5.1), ascites/edema (13.0/3.4), fever (12.4/1.0), and rash (11.5/1.4), with AE grade 5 observed in 9 patients (0.9%) (liver injury 4, interstitial pneumonia 3, esophageal varices bleeding 1, and colitis 1). Immune-related AE, which required steroids, was occurred in 148 (15.4%).

Conclusion

In the clinical practice of Japanese u-HCC patients numbering over 1000, AB showed favorable therapeutic results and similar safety to those of the IMbrave150 trial (median observation period 8.6 months). The prognostic improvement effect of initial line use might be better than that of subsequent lines. To obtain a better prognosis, the introduction of AB is recommended in patients with better hepatic reserve function, if possible.

Introduction

Percutaneous liver biopsy (PC-LB) is the gold standard for the study of chronic liver disease. However, it is limited to patients with appropriate clinical and hematological conditions. Transjugular liver biopsy (TJ-LB) represents a less invasive yet less available technique. Endoscopic ultrasound-guided liver biopsy (EUS-LB) has emerged as a minimally invasive readily available technique. To the best of our knowledge, no network meta-analysis has compared LB quality and related adverse events among these techniques.

Aims & Methods

A systematic search was run in PubMed, Embase, Web of Science and Cochrane. The search included studies from inception to November 2023, in adult patients, which compared at least two of the following techniques: EUS-LB, PC-LB or TJ-LB. The analyzed endpoints were mean total sample length (TSL), mean number of complete portal triads (CPT), rate of appropriate sample for diagnosis, sample fragmentation and major adverse events (hematomas, bleeding, perforation, death). There was no distinction regarding study design, biopsy needle type or assistance with additional imaging methods. The studies with insufficient data, without any reported endpoint, or case series were excluded. The PC-LB was the reference. Data was analyzed in Rv4.0.

Results

Over the last thirty years (1993 to 2023), 21 original studies were analyzed being: 18/21 full manuscripts; 15/21 retrospective, 3/21 prospective, 3/21 randomized clinical trials (RCT); 11/21 EUS-LB, 21/21 PC-LB and 16/21 TJ-LB; 5/21 EUS-LB vs PC-LB, 10/21 PC-LB vs TJ-LB, and 6/21 compared the three techniques. We scrutinized 620 EUS-LB patients, 3347 PC-LB, and 1901 TJ-LB. TSL pooled mean for EUS-LB, PC-LB, and TJ-LB was 28.6 ± 10.6 mm, 23.3 ± 13.5 mm, and 15.7 ± 9.0 mm, respectively. Pooled rate of appropriate sample for diagnosis was 96.6%, 89.2%, and 85.4%, with a major adverse events pooled rate of 4%, 2.9%, and 3.5%, respectively. Between 14 studies and 24 pairwise comparisons, TSL EUS-LB mean was 0.17 mm longer (p=.932), but TJ-LB 4.93 mm shorter (p=.0025) (I²=95%). Between 3 studies and 5 pairwise comparisons, relative risk (RR) of sample fragmentation was significantly higher for EUS-LB (RR 4.55; 95% CI 2.72 – 7.61; p<.001) and TJ-LB (RR 2.72; 95% CI 1.54 - 4.80; p<.001) (I²=0%). There was not significant difference among mean number of CPT (I²=97.3%), rate of appropriate sample for diagnosis (I²=48.7%) or major adverse events (I²=10.5%).

Conclusion

EUS-LB quality is comparable to PC-LB and superior to TJ-LB in terms of TSL. These techniques are comparable in terms of the mean number of CPT, rate of appropriate sample for diagnosis, and major adverse events. Further original studies are needed to define the sample fragmentation rate of the aforementioned.

References

McCarty TR, Bazarbashi AN, Njei B, Ryou M, Aslanian HR, Muniraj T. Endoscopic Ultrasound-Guided, Percutaneous, and Transjugular Liver Biopsy: A Comparative Systematic Review and Meta-Analysis. Clin Endosc. 2020 Sep;53(5):583-593. doi: 10.5946/ce.2019.211. Epub 2020 Sep 29. PMID: 33027584; PMCID: PMC7548145.
Chandan S, Deliwala S, Khan SR, Mohan BP, Dhindsa BS, Bapaye J, Goyal H, Kassab LL, Kamal F, Sayles HR, Kochhar GS, Adler DG. EUS-guided versus percutaneous liver biopsy: A comprehensive review and meta-analysis of outcomes. Endosc Ultrasound. 2023 Mar-Apr;12(2):171-180. doi: 10.4103/EUS-D-21-00268. PMID: 36204798; PMCID: PMC10237604.

Introduction

Gastric cancer is the 5^th most common cancer globally(1). Europe's Beating Cancer Plan recognises the urgent need for a gastric cancer screening strategy(2). One promising approach, outlined in the Maastricht VI/Florence consensus report, suggests integrating screening modalities for gastric cancer, such as gastroscopy with colorectal cancer screening (3). This method holds the potential for cost-saving benefits through combined screening efforts (4).

Aims & Methods

We aimed to determine the prevalence of preneoplastic and neoplastic lesions in a high-risk age group, in those who underwent gastroscopy at the time of colonoscopy. Our secondary aims were to determine a)the quality of endoscopy performed and b) the endoscopic burden for pathology that required follow-up.
This was a single-centre review and audit of key performance indicators in a colorectal cancer screening centre. The age group targeted was 50-74, i.e. the target group for colon cancer screening in Europe. We included those undergoing colonoscopy for polyp surveillance or as part of the national colon cancer screening programme. Participants with red flag symptoms (iron deficiency anaemia, weight loss, dysphagia), family history of gastric cancer, established diagnosis of Barrett’s, intestinal metaplasia, dysplasia or who had a gastroscopy in the last 3 years were excluded. The sample size required for a 95% confidence interval with a presumed positivity rate of 5-7% was 101. Descriptive statistics, correlations and associations were examined using Stata software.

Results

101 patients were included; the median age was 59;38% were male. Indications for gastroscopy included abdominal pain (45%), chronic reflux (37%), chronic dyspepsia (7%) and other (9%). All patients had a technically complete gastroscopy (D2 intubation rate 100%, retroflexion 100%), the median procedure length was 7 minutes(range 4-21). 93% of patients had a macroscopic finding at the time of gastroscopy. Findings included gastritis(chronic superficial, chemical)(60%), hiatus hernia (50%), oesophagitis (28%), duodenitis (24%), gastric body polyps (10%), Barrett’s mucosa (8%), benign gastric or duodenal ulceration(9%), Schatzki ring (4%), erosions (4%), intestinal metaplasia (IM)(1%), oesophageal candidiasis (1%) and varices (1%). 59% had biopsies taken from two topographical sites as per MAPS guidelines. On biopsy, Helicobacter pylori infection was found in 15% (15/101), 7% had intestinal metaplasia(IM); no atrophy, dysplasia or cancer was detected. In those with IM who had MAPS biopsies (5/7), all were focal IM. In those with suspected Barrett’s (n=8), 88% had biopsies taken in accordance with the Seattle protocol and the Prague classification was used in 50% of cases. Additional pathology encountered included histological evidence of antral gastritis (56%), body gastritis (53%), reflux oesophagitis (21%), Barrett’s without dysplasia (4%), duodenitis (3%), and eosinophilic oesophagitis (1%). There was no statistical difference in age (p<0.82) or gender (p<0.32)in those with preneoplastic changes on gastroscopy.

Conclusion

11% of individuals within the target age bracket exhibited a pre-neoplastic condition on gastroscopy and/or histology (i.e. gastric intestinal metaplasia, gastric atrophy or Barrett's oesophagus), a further 15% were diagnosed and treated for Helicobacter pylori infection, the leading cause of gastric cancer. Among these cases, 4-7% necessitated subsequent surveillance gastroscopy. Our findings support the role of dual endoscopic screening with quality gastroscopy as a potential strategy for gastric cancer screening.

References

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
2. Commission E. Europe's Beating Cancer Plan - Communication from the commission to the European Parliament and the Council. 2021.
3. Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022.
4. Libanio D, Antonelli G, Marijnissen F, Spaander MC, Hassan C, Dinis-Ribeiro M, Areia M. Combined gastric and colorectal cancer endoscopic screening may be cost-effective in Europe with the implementation of artificial intelligence: an economic evaluation. Eur J Gastroenterol Hepatol. 2024;36(2):155-61. doi: 10.1097/MEG.0000000000002680. Epub 2023 Nov 15.

Introduction

Arsenic, a potent environmental toxin, has been widely reported to cause significant health problems, including liver damage and disturbances in the metabolic processes. One of the lesser-understood facets of arsenic toxicity is its impact on gut microbiota, the community of microorganisms living in the intestinal tract, which plays a crucial role in host metabolism and overall health. Previous studies have indicated that arsenic exposure can alter the composition of gut microbiota, potentially affecting the host’s metabolism of arsenic and exacerbating its toxic effects. Despite ongoing research, the mechanisms underlying the interaction between arsenic exposure, gut microbiota changes, and arsenic metabolism remain inadequately defined.

Aims & Methods

The primary objective of this study was to elucidate the dynamics of gut microbiota changes under varying levels of arsenic exposure and to understand how these changes affect arsenic metabolism and subsequent liver toxicity. We used C57BL/6 mice as a model system, exposing them to 0, 5, or 10 ppm sodium arsenite (NaAsO2) in their drinking water over a period of six months. We conducted a comprehensive analysis of the gut microbiota, focusing on folic acid (FA)/vitamin B12 (VB12)- and butyrate-synthesizing communities. Additionally, molecular interactions between arsenic and methionine synthase (MTR), an enzyme crucial for FA/VB12 utilization, were assessed using 3D molecular simulations and biochemical assays. The intervention model involved supplementation of FA and VB12 to evaluate their protective effects against arsenic-induced disturbances.

Results

Exposure to NaAsO2 significantly altered gut microbiota, with a notable increase in the abundance of FA/VB12- and butyrate-synthesizing microbiota. This shift was hypothesized to compensate for the disrupted utilization of these nutrients due to arsenic exposure. In higher arsenic exposure levels, however, the microbiota changes were inconsistent, suggesting a potential threshold beyond which the compensatory mechanism may be overwhelmed. Biochemical assays confirmed that arsenic binds to MTR, disrupting its function and further impacting FA/VB12 metabolism. The interaction was substantiated by SEC-UV-DAD and fluorescence-labeled arsenic studies, which demonstrated that arsenic directly interacts with MTR in both non-cellular and cellular systems. Our intervention model using FA and VB12 supplementation showed that it was possible to mitigate the disturbances in gut microbiota, restore MTR levels, enhance arsenic metabolism, and reduce liver injury.

Conclusion

This study provides significant insights into the interaction between arsenic exposure and gut microbiota. We demonstrated that changes in gut microbiota are not merely a consequence of arsenic exposure but are intricately linked to the metabolic processes affected by arsenic, particularly through the disruption of MTR function. The supplementation of FA and VB12 proved effective in blocking these disturbances, suggesting potential therapeutic strategies to combat arsenic toxicity. The findings emphasize the importance of considering gut microbiota in the management and treatment of arseniasis and underscore the complex interplay between environmental toxins, gut microbiota, and host metabolism. Future studies should focus on further delineating the specific pathways and mechanisms by which microbiota influence arsenic metabolism and exploring the potential for microbiota-targeted therapies in arsenic-related diseases.

Introduction

Esophageal variceal bleeding is a serious and fatal complication of cirrhosis. Currently, efficient noninvasive monitoring strategies are lacking. By applying artificial intelligence (AI) to computed tomography (CT) imaging, we developed an innovative tool to meet clinical needs.

Aims & Methods

This is an ambispective cohort study conducted at West China hospital between April 2021 and December 2021, patients underwent endoscopy and enhanced CT were registered. Furthermore, 97 patients with radiomic and hepatic venous pressure gradient data were enrolled from a portal hypertension database. High-risk esophageal varices (HREV) were defined as either moderate-severe varicose (HREV-1) or EV requiring intervention (HREV-2). Deep learning was used to develop segmentation and EV quantification models. The EV bleeding prediction model was established using least absolute shrinkage and selection operator (LASSO) regression and logistic regression analysis. The area under the curve (AUC) was calculated for efficiency evaluation. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2300069865) and is completed.

Results

A total of 2291 patients in the retrospective (n=780) and prospective (n=1511) cohorts were included. The internal and external validation cohort AUCs were 0.976 and 0.951 for EV vs. non-EV, 0.986 and 0.951 for HREV-1, and 0.978 and 0.898 for HREV-2, respectively. We found that volume (p=0.0348) and AI-10 (p=0.0196) were closely related to portal pressure. We further analyzed the AI features and bleeding events for patients with cirrhosis in the retrospective (n=254) and prospective (n=569) cohorts and applied the EV bleeding prediction model (validation cohort AUCs of 0.669, 0.701 and 0.705 at 1, 3, and 6 months, respectively), which was not inferior to that of endoscopic signs (p > 0.05).

Conclusion

Enhanced CT assisted by AI is a promising noninvasive strategy for quantifying EV, recognizing HREV and predicting short-term bleeding risk and has the potential to replace simple gastroscopy for diagnosis or monitoring. This approach could decrease unnecessary gastroscopy to some extent.

Disclosure

The authors have declared no competing interests.