Introduction

Gastric intestinal metaplasia (GIM) is a known premalignant lesions of gastric cancer (GC). Several factors have been associated with the progression of GC such as family history, smoking and increased BMI. Dietary factors such as the consumption of meat, salt and alcohol are also linked to GC progression. However, the intricate relationship between dietary factors and the progression of GIM remains poorly understood. The aim of this prospective cohort study was to identify dietary factors for GIM progression in a low incidence area.

Aims & Methods

The Progression and Regression of Precancerous Gastric Lesions (PROREGAL) study prospectively included patients with GIM who underwent endoscopic surveillance from September 2009 to February 2024. GIM stage was determined by the Operative Link on Gastric Intestinal Metaplasia (OLGIM) criteria. Disease progression was based on the increase in OLGIM, comparing the baseline score to at least two follow-up (FU) endoscopies. If only one FU endoscopy was conducted, the baseline was compared to this single FU examination. Comprehensive data on family history, lifestyle factors, and dietary habits were collected through structured questionnaires. Helicobacter pylori (H. pylori) infection status was determined by pathology. Multivariate logistic regression analysis was used to determine risk factors.

Results

In total 312 patients were included, with a median FU of 54 months (median age: 61 years, 50.3% male) of which 112 patients (35.9% ) showed GIM progression (7.6% to stage I, 27.6% to stage II, 46.7% to stage III and 18.1% to stage IV), with six patients (1.9%) developing high-grade dysplasia or GC. A positive family history (first or second degree) was present in 103 (30.6%) cases. High dietary salt consumption (OR 1.67; 95% CI 1.05–2.68, P=0.04), meat ≥6 servings per week (OR 1.25; 95% CI 1.07–1.46, P=0.004) smoking (OR 1.76; 95%CI 1.04–2.68), autoimmune gastritis (OR 2.49; 95%CI 1.04–5.83) and having a positive first-degree family member with GC (OR 2.01; 95%CI 1.20–3.52) significantly associated with GIM progression. Factors like fish intake, alcohol consumption, prepared meal consumption, fruit and vegetable intake, autoimmune gastritis (AIG), extensive GIM, vitamin intake, Body Max Index (BMI) and history of H. pylori infection showed no significant association.

Conclusion

Increased consumption of meat and salt is significantly associated with GIM progression, suggesting that dietary risk factors for GIM progression are similar in low-incidence Western countries and high-incidence regions.

References

1. Bray F, Laversanne M, Sung H et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 2024; 74: 229-263. doi:10.3322/caac.21834
2. Chen Y-C et al. Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022. Gastroenterology 2024; 166: 605-619. doi:10.1053/j.gastro.2023.12.022
3. Shin WS et al. Updated Epidemiology of Gastric Cancer in Asia: Decreased Incidence but Still a Big Challenge. Cancers 2023; 15: 2639. doi:10.3390/cancers15092639
4. Fock KM, Ang TL. Epidemiology of Helicobacter pylori infection and gastric cancer in Asia. Journal of Gastroenterology and Hepatology 2010; 25: 479-486. doi:10.1111/j.1440-1746.2009.06188.x
5. Allemani C, Weir HK, Carreira H et al. Global surveillance of cancer survival 1995–2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2). The Lancet 2015; 385: 977-1010. doi:10.1016/s0140-6736(14)62038-9
6. Huang RJ, Choi AY, Truong CD et al. Diagnosis and Management of Gastric Intestinal Metaplasia: Current Status and Future Directions. Gut and Liver 2019; 13: 596-603. doi:10.5009/gnl19181
7. Poorolajal J et al. Risk factors for stomach cancer: a systematic review and meta-analysis. Epidemiology and Health 2020; 42: e2020004. doi:10.4178/epih.e2020004

Introduction

Prophylactic total gastrectomy (PTG) is the definitive treatment for hereditary diffuse gastric cancer syndrome (HDGC). Endoscopic surveillance informs the requirement and optimal timing to surgery. However, endoscopic recognition of early signet ring cell carcinoma (SRCC) remains challenging. In this study, we aimed to develop and prospectively validate a user-friendly diagnostic framework with machine-learning to support endoscopists in accurate identification of early SRCC during surveillance in HDGC individuals.

Aims & Methods

We retrospectively analysed 147 HDGC individuals undergoing endoscopic surveillance to evaluate the diagnostic accuracy of endoscopic criteria (Cambridge criteria), develop a clinical decision tree (cDT) to better apply the criteria based on machine leaning, and investigate its clinical significance. We then prospectively validated cDT in 66 CDH1 pathogenic-variant carriers. The inter-observer agreement and diagnostic accuracy of Cambridge criteria and cDT were assessed through multi-reader multi-case study.

Results

Retrospective analysis of 537 endoscopies showed Cambridge criteria achieved 82.8% (48/58) sensitivity and 78.2% (140/179) specificity for SRCC diagnosis. The presence and number of neoplastic pale areas are independent predictors of higher cancer burden in HDGC individuals. In prospective study, cDT had 77.8% (21/27) sensitivity and 90.7% (49/54) specificity. The cDT significantly improved average sensitivity among non-experts from 66.7% to 72.5% and 87.5%, and among experts from 74.1% to 80.0% and 91.7% (P = 0.03).

Conclusion

We developed and validated a practical endoscopic framework to enhance SRCC assessment during HDGC endoscopic surveillance.

Introduction

Hereditary diffuse gastric cancer (HDGC) associated with CDH1 germline pathogenic variants (PV), carries a high lifetime risk of signet ring cell carcinoma (SRCC). Clinical and molecular events driving progression from early SRCC to advanced cancer are elusive, therefore there is uncertainty to whom and when to recommend risk reducing total gastrectomy (RRTG). We hypothesise a high number of early SRCC lesions (SRCC burden) could be a risk factor for progression to clinical gastric cancer. This study aimed to identify predictors of SRCC burden and provide evidence to modify surveillance intervals.

Aims & Methods

We analyzed data from 53 CDH1 PV carriers who underwent RRTG prospectively recruited between Jan 2006 and Dec 2024 (RRTG dataset) and a separate cohort of 95 CDH1 carriers with ≥2 surveillance endoscopies and 0-2 positive biopsies at baseline (endoscopy dataset). Targeted biopsies (TB) and systematic random biopsies (RB) were obtained using the Cambridge protocol. Multivariable negative binomial regression was used to assess the association of clinical (age, sex, family history, ethnicity, CDH1 variant type) and endoscopic factors (mean number of positive TB and RB per endoscopy) with SRCC burden in RRTG specimens. A logistic regression model with significant predictors was trained to classify patients into low (≤20 foci) and high (>30 foci) cancer burden, validated over 1,000 iterations. Temporal trends in biopsy findings were analyzed using linear mixed-effects models in endoscopy dataset. Surveillance effectiveness at 6- and 12-month intervals was compared in a subset of 38 patients with at least one positive endoscopy followed by subsequent surveillance.

Results

Among 53 RRTG patients (median: 3 surveillance endoscopies over 19 months), 47 (90%) had pT1aN0M0 cancer, and 6 (11%) had pT0N0M0. The mean number of SRCC foci on RRTG specimens was 13, with a median of 33 (IQR: 2-37) and a range of 0 to 273. Among clinical factors, whereas the average number of positive TB (p = 0.001) and RB (p < 0.001) per endoscopy were independent predictors. The model based on endoscopy factors achieved an AUC of 0.88 (0.87, 0.89) for predicting cancer burden under RRTG. No significant trend in biopsy positivity over time was observed (Estimate = 0.0046, p = 0.176). Extending surveillance intervals from 6 to 12 months in patients with low-level positivity did not significantly reduce detection of increased positive biopsies (22% vs. 19%, p = 0.78). Furthermore, using ≥3 positive biopsies as a trigger for recommending RRTG, only 6 patients (16%) met this threshold. The median time after the first positive endoscopy to meeting this criterion was 9 months (95% CI: 0-29) under the 6-month surveillance strategy and 12 (95% CI: 3-33) months under the 12-month surveillance strategies.

Conclusion

Endoscopic surveillance using targeted and random biopsies by experienced endoscopists provides a reliable estimate of SRCC burden in HDGC. Our findings suggest that extending surveillance intervals and delaying surgery in patients with low early SRCC burden is clinically safe.

Clinical Case Summary

Our patient was a 66yr Chinese man who was treated for active Chronic Hepatitis B from 2009 with Lamivudine, Adefovir and then switched to Tenofovir from 2020 with long term undetectable Hepatitis B viral load (HBV VL) and normal Liver function tests. His ultrasound liver was normal and Fibroscan 6.9kpa in 2021. Hepatitis B Surface quantification was 87 IU/ml. ALT 28.
The patient was enrolled in a research trial which randomized him to stopping Tenofovir with close follow up.
At week 4 after stopping Tenofovir, his HBV VL became detectable at 2.53log and ALT 31.
At week 8, his HBV VL increased to 5.55log and ALT 35.
At week 10, HBV VL was 6.85, ALT 384, Bilirubin and INR normal. HBeAg remained negative and the patient remained asymptomatic.
He was promptly restarted on Tenofovir but his ALT continued to rise and peaked at 832 at week 12 before gradually returning to normal as did his Hepatitis B viral load.
At week 13, he developed tingling over his hands and feet.
At week 14, he was admitted for clumsiness with reduced sensation over the feet and hands. He had no other systemic symptoms suggestive of any infections.
Examination revealed subjective reduction in sensation over the distal peripheral limbs. Power was normal but reflexes were absent over the ankles and knees.
MRI brain was normal.
Lumbar puncture showed high CSF protein 0.7gL but normal cell count. Nerve Conduction study (NCS) reported acute inflammatory demyelinating polyneuropathy.
EMG was unremarkable.
A probable diagnosis of GBS was made.
His ALT was down to 304 and HBV VL 3.82 log.
NCS repeated 2 months later and showed similar inflammatory demyelinating polyneuropathy.
NCS repeated 4 months later showed significant improvement which confirmed a diagnosis of GBS
1 year from his first presentation, he recovered fully.
Only 7 cases of Hepatitis B related GBS have been reported in the literature. Our case highlights GBS resulting from Hepatitis B flare

References

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Introduction

Vedolizumab (VDZ) is a monoclonal antibody therapy approved in China in 2020 for the treatment of patients with inflammatory bowel disease (IBD; Crohn's disease [CD] and ulcerative colitis [UC])² who were intolerant to conventional therapies.¹ VDZ has a unique, gut-selective, anti-lymphocyte trafficking (GSALT) mechanism of action.³ However, data on the efficacy and safety of VDZ in Chinese patients with IBD in the real-world setting are limited.⁴ This study evaluated the safety of VDZ in adult patients with IBD.

Aims & Methods

VALUE (NCT04872491) was a multicenter, single-arm, prospective, observational study to evaluate the safety of VDZ in adult Chinese patients with IBD (N=500) over a maximum observation period of 72 weeks. Incidence of adverse events (AEs), serious AEs (SAEs), treatment-related adverse drug reactions (ADRs), and AEs of special interest (AESIs) was evaluated. This was the final analysis of the VALUE study conducted in patients with IBD.

Results

A total of 500 patients (UC: n=409; CD: n=91) received VDZ 300 mg. Mean (±standard deviation) age of patients was 44.3 (±15.2) years, and 61.4% (n=307) were male. The mean duration for VDZ exposure was 414 days (UC: 416 days; CD:407 days). A total of 500 patients developed 674 AEs (Table), and the most frequent AEs were infections and infestations (I&I; UC: 115 [28.1%]; CD: 24 [26.4%]), followed by gastrointestinal disorders (GIDS; UC: 87 [21.3%]; CD: 18 [19.8%]). Incidence rates of AEs (/patient-years) were 1.2 and 1.0 in patients with UC and CD, respectively. Overall, 13 (3.2%) patients with UC and 10 (11.0%) with CD had AEs leading to study discontinuation. SAEs were observed in 78 patients with UC and 18 with CD (Table). A total of 19 AESIs were reported by patients with UC and 9 AESIs by those with CD, with the most common AESIs being I&I (UC: 13 [3.2%]; CD: 4 [4.4%]) and malignancy (UC: 3 [0.7%], CD: 2 [2.2%]). The most common I&I disorders reported by patients with UC and CD were Clostridium difficileinfection (4 [1.0%]) and pneumonia (1 [1.1%]), respectively. Overall, 17 (4.2%) patients with UC and 7 (7.7%) with CD had at least 1 AESI. A total of 91 and 15 treatment-related ADRs were observed in patients with UC and CD, respectively; I&I were the most frequently documented ADRs to VDZ treatment (Table). A total of 10 (UC: 5 [1.2%]; CD: 5 [5.5%]) patients treated under concomitant IBD advanced therapy (CIBDAT) experienced a total of 16 AEs (UC: 9; CD: 7), with the most common AEs being I&I (UC: 1 [20.0%]; CD: 2 [40.0%]) and GIDS (UC: 3 [60.0%]; CD: 1 [20.0%]) with CIBDAT. No deaths were reported during the study.

Conclusion

The VALUE study indicated that VDZ was well tolerated in Chinese patients with IBD, with no new safety concerns.

References

1. Scribano ML. World J Gastroenterol. 2018; 24: 2457-2467.
2. Yamamoto S et al., Cureus. 2024;16: e59691.
3. Soler D et al. J Pharmacol Exp Ther. 2009; 330: 864-875.
4. Baili C et al. Am J Gastroenterol. 2023; 118: S213-S214.

Disclosure

This study was funded by Takeda (China) International Trading Co. Ltd. Li Li, Haiyan Zhang, Chengxia Liu, and Xiaomei Sun have no conflicts of interest. Xiaoyu Qian and Fang Zhou are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honorariums from Takeda China, AstraZeneca China, Xian Janssen, and Eisai China.
Medical writing support for the development of this abstract under the direction of the authors was provided by Vibhuti Singh, Ph.D., of Cactus Life Sciences (part of Cactus Communications), funded by Takeda (China) International Trading Co., Ltd.

Clinical Case Summary

A 54-year-old male with chronic myeloid leukemia (CML) diagnosed in May 2015, on Imatinib since April 2023, presented in October 2024 a severe anemia (Hb 5.2 g/dL [13-17]). Investigations done at that time, including bone marrow analysis, hemolysis workup and a FIT test were normal. An abdominal CT scan was also done at that time and was also normal.. In December 2024, the patient reported two weeks of melena. A bidirectionnel endoscopy didn’t show any lesion. CT scan revealed hepatomegaly and gallstones, without any GI mass.
Video capsule endoscopy showed active jejunal bleeding without being able to identify the underneath lesion. Enteroscopy revealed two ulcerated jejunal lesions of around 2 cm in diameter with an adherent clot, one meter from the papilla, [Figure 1,2]. Surgical resection was then performed [Figure 3]. Histology confirmed epithelioid angiosarcoma with submucosal infiltration, numerous mitoses, endolymphatic tumor emboli, and ERG+, cytokeratine AE1/AE3+ immunoprofile. Resection margins were clear; 0/3 lymph nodes were involved. [Figure 4a-b-c-d] As part of the metastatic workup, brain MRI showed multiple cerebral metastases.
Following the diagnosis, the treatment plan consisted of paclitaxel in combination with bevacizumab (Avastin).
This case illustrates the diagnostic challenge of unexplained anemia in hematologic patients, particularly when standard evaluations fail to identify a clear cause. In this instance, gastrointestinal bleeding ultimately revealed a rare small bowel malignant lesion—epithelioid angiosarcoma. While epithelioid angiosarcoma has no established association with chronic myeloid leukemia (CML) or its treatment, it is worth noting that the use of tyrosine kinase inhibitors may obscure the clinical presentation of angiosarcoma. This is due to their antiangiogenic effects, which can alter vascular structures and potentially delay diagnosis. Therefore, high clinical suspicion remains essential.

References

Figure 1,2 : Enteroscopy revealing ulcerated jejunal lesion with an adherent clot. Images obtained during enteroscopy performed at Hôtel-Dieu de France University Hospital, Beirut, Lebanon.
Figure 3 : Resected jejunal segment showing two hemorrhagic polypoid tumors, one marked with a hemostatic clip. The lesions correspond to an ulcerated angiosarcoma. Image obtained post-surgical resection at Hôtel-Dieu de France University Hospital, Beirut, Lebanon.
Figure 4a : Histological appearance of epithelioid angiosarcoma H&E stain, high magnification
Figure 4b : Histological appearance of epithelioid angiosarcoma H&E stain, intermediate magnification
Figure 4c : Histological appearance of epithelioid angiosarcoma H&E stain, low magnification
Figure 4d : Histological appearance of epithelioid angiosarcoma ERG nuclear immunostain, intermediate magnification
Figure 4e : Histological appearance of epithelioid angiosarcoma Cytokeratin AE1/AE3 immunostain, intermediate magnification

Clinical Case Summary

We present a case, which demonstrates endoluminal vacuum (EndoVac) therapy as an efficient technique when used for postoperative esophago-jejunal anastomotic leakage. A 59-year-old male, who underwent a total gastrectomy with esophago-jejunal Roux-en-Y anastomosis for stomach adenocarcinoma, presented with abdominal pain, tachycardia, fever and dyspnea a few days after the operation. A CT demonstrated a large anastomotic leakage in the esophago-jejunoanastomosis. An upper endoscopy was performed, revealing an anastomotic defect with a diameter up to 20mm. A 120mm fully covered esophageal stent was inserted. The stent was fixated with three 16mm clips. Due to clinical deterioration a follow up CT was performed. The images showed proximal migration of the stent with a perianastomotic inflammatory cavity. The stent was retrieved and 2.5L of pus-like fluid was evacuated, followed by placement of EndoVac System. During the procedure, a 15fr PEG-J feeding tube was placed, ensuring enteral nutrition. Additionally VATS was performed immediately after the endoscopy and two redon drains were placed.
Four EndoVac sponges were exchanged in a period of 12 days, during which a significant clinical improvement was observed and the patient was discharged shortly after. Eight weeks later gastroscopy and CT were performed with no evidence of a fistula and complete recovery of the patient, the PEG-J was removed. We demonstrate with our case that EndoVac therapy is an effective method in managing postoperative esophageal leaks and it should be considered as an initial technique when dealing with such complications.

References

Endoscopy photo of the ansatomotic leak
Endoscopy photo EndoVac
Endoscopy photo of the PEG-J
Endoscopy photo of the final result