Introduction

Patients with gastric intestinal metaplasia (GIM) are at an increased risk of developing gastric cancer (GC). The histological Operative Link on Gastric Intestinal Metaplasia (OLGIM) classification aids in risk stratification. The recently developed endoscopic grading of GIM (EGGIM) may accurately predict the OLGIM stage. This study aimed to evaluate the diagnostic accuracy of EGGIM in assessing histological GIM using data from two large, prospective European consortia.

Aims & Methods

Interim data were derived from the Artificially Intelligent Diagnostic Assistant (AIDA) and Towards Gastric Cancer Screening Implementation in the European Union (TOGAS) consortia, both part of a European Horizon programme focused on gastric cancer prevention. Patients in AIDA underwent oesophagogastroduodenoscopy (OGD) for GIM surveillance or treatment of neoplastic lesions, while participants in TOGAS (aged 50–74) were offered an OGD during screening colonoscopy or polyp surveillance. Procedures were performed at eight academic centres by both expert and non-expert endoscopists, using high-resolution white-light endoscopy and virtual chromoendoscopy. The EGGIM score (range 0–10) was based on the extent of GIM (0: 0%, 1: ≤30%, 2: >30% of mucosa) across five anatomical sites: the lesser and greater curvatures of the antrum and corpus, and the incisura. Targeted biopsies were taken if GIM was suspected; otherwise, random biopsies were collected according to the Sydney system to determine the OLGIM stage. Healthy controls and GIM patients with an EGGIM score ≥1 but OLGIM stage 0 were also included. ROC curve and Spearman analyses assessed the diagnostic and ordinal correlation between EGGIM and OLGIM stages III–IV.

Results

A total of 252 patients were included (median age 60 years, IQR 9; 57.4% female): 91 from the TOGAS study (75 cancer screening, 16 polyp surveillance) and 161 from AIDA (117 GIM surveillance, 21 neoplasia treatment, 23 healthy controls). OLGIM staging identified 89 (35.3%) patients in stage 0, 74 (29.4%) in stage I, 49 (19.4%) in stage II, 35 (13.9%) in stage III, and 5 (2.0%) in stage IV. The area under the ROC curve for EGGIM in detecting OLGIM III/IV was 0.90 (95% CI 0.79–0.93, p < 0.001), with an optimal cut-off at EGGIM ≥5 (sensitivity 85%, specificity 89%).

Conclusion

Our findings prospectively validate the EGGIM score across two large European cohorts. This scoring system may serve as a practical tool to streamline gastric cancer surveillance by reducing the need for biopsies and enhancing endoscopic risk stratification.

References

Esposito G, Pimentel-Nunes P, Angeletti S, et al. Endoscopic grading of gastric intestinal metaplasia (EGGIM): a multicenter validation study. Endoscopy. 2019;51(6):515-521. doi:10.1055/a-0808-3186

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

none

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

Introduction

Gastric cancer remains a major global cause of cancer mortality. Early detection and accurate risk stratification are crucial for improving prognosis. Noninvasive, affordable serum tests are essential for mass screening. We compared the updated ABC method (pepsinogen I/II and gastrin-17) and a novel gastric cancer scoring system (“new scoring system”) regarding their effectiveness in screening early gastric cancer and precancerous lesions, risk stratification, and missed diagnosis prevention.

Aims & Methods

From April to November 2024, 7,304 asymptomatic individuals from Yuhang District, Hangzhou, China, participated in community-based screening. Serum pepsinogen I (PGI), PGII, PGI/II ratio (PGR), gastrin-17 (G-17), and H. pylori antibody were tested. Participants were stratified into low-, medium-, or high-risk groups using the ABC method and the new scoring system. A total of 654 medium- and high-risk participants underwent endoscopy and histopathology. Detection rates of gastric cancer, intraepithelial neoplasia, and atrophic gastritis were compared. Missed diagnosis rates in low-risk groups were analyzed assuming no endoscopy.

Results

The ABC method classified 90.55% as low-risk, 7.69% medium-risk, and 1.75% high-risk. The new scoring system classified 59.42% as low-risk, 32.67% medium-risk, and 7.91% high-risk. Endoscopy detected 11 gastric cancers (1.68%, 10 early-stage), 21 intraepithelial neoplasias (3.21%), and 98 atrophic gastritis cases (14.98%).
Gastric cancer detection rates in medium/high-risk groups were similar: ABC 1.58% (3/190), new scoring 1.77% (10/565) (p=1.000). Atrophic gastritis rates were comparable (ABC 14.21%, new scoring 15.04%, p=0.872). In the high-risk subgroup, the new scoring system detected significantly more atrophic gastritis cases (29.87% vs ABC 16.33%).
In low-risk groups, the ABC method would miss 8 of 11 gastric cancers (72.73%) without endoscopy; the new scoring system would miss only 1 case (9.09%, p=0.009). ROC analysis showed higher AUC for the new scoring system (0.60 vs 0.51). Decision curve analysis indicated superior net clinical benefit for the new scoring system at threshold probabilities above 0.2. The new scoring system showed higher sensitivity for early-stage disease detection, whereas ABC had slightly higher specificity.

Conclusion

Both systems showed similar performance in detecting gastric cancer and precancerous lesions among medium- and high-risk populations. The new scoring system significantly reduced missed diagnoses in low-risk groups and improved identification of high-risk precancerous conditions. Incorporating ROC, DCA, and accuracy metrics, the new scoring system offers enhanced flexibility for risk stratification, making it potentially more effective for population-based gastric cancer screening, especially in resource-limited settings. Further validation in larger cohorts is warranted.

Disclosure

Nothing to disclose.

Introduction

Colorectal cancer surveillance recommendations for individuals with Lynch Syndrome (LS) differ between professional associations and the data on interval colorectal cancer (I-CRC) and interval advanced polyps (I-AP) are limited. We aimed to measure the rate of I-CRC and I-AP within a surveillance program.

Aims & Methods

Retrospective study involved individuals with LS who participated in CRC surveillance program at Clalit Health hospitals, Israel. The main outcomes were the rates of I-CRC and I-AP ≤36 months, categorized by 12-month intervals. Included only colonoscopies with adequate preparation. I-CRC and I-AP (≥10 mm or containing high-grade dysplasia or villous histology) were defined as interval advanced neoplasia (I-AN).

Results

The cohort included 342 individuals, 52.3% females, with a median age at data analysis of 49.0 (IQR 37.7-64). At interval ≤ 12 months, there were 7 cases of I-CRC [6/142 (4.2%) of MSH2; 1/46 (2.2%) of MLH1] and 13 cases of I-AP (10/142 (7.0%) of MSH2, 2/46 (4.3%) of MLH1, 1/136 (0.7%) of MSH6]. At 12-24 months, there were 3 cases of I-CRC [2/142 (1.4%) of MSH2, 1/136 (0.7%) of MSH6] and 10 cases of I-AP [8 /142 (5.6%) of MSH2, 1/46 (2.2%) of MLH1, 1/136 (0.7%) of MSH6]. At 24-36 months, there were 3 cases of I-CRC [2/142 (1.4%) of MSH2, 1/18 (5.6%) of PMS2] and 4 cases of I-AP [1 /142 (0.7%) of MSH2, 3/136 (2.2%) of MSH6]. Of all I-CRC, four were diagnosed at stage 3 [4/342 (1.2%)], all at interval ≤24months [3-MSH2, 1-MSH6]. Increasing age and path_MSH2 were significantly associated with I-AN.

Conclusion

Extending surveillance colonoscopy intervals could result in significant rates of I-CRC and I-AP. Diagnosis of I-CRC at advance stage can occur at interval less than 24 months.