Gastric Cancer Screening: Intention to Adhere and Patients' Perspective.

BACKGROUND AND AIMS: Gastric cancer (GC) is the third cause of cancer mortality worldwide. A screening strategy that combines an upper gastrointestinal endoscopy (UGIE) with a screening colonoscopy may be cost-effective in intermediate-risk regions. This study aimed to evaluate the intention to adhere to combined endoscopic screening and assess knowledge of GC symptoms, risk factors, and barriers to screening. METHODS: Cross-sectional study enrolling individuals eligible for CRC screening in northern Portugal, where a populational fecal occult blood test (FOBT) program is implemented. The validated PERCEPT-PREVENT tool was applied across three groups: (a) not yet invited to CRC screening, (b) FOBT-positive referred to colonoscopy, and (c) primary colonoscopy screening. RESULTS: A high acceptance rate was observed for combined endoscopic screening (94%; n = 264) [not yet invited to CRC screening 98% (n = 90) vs. FOBT-positive referred to colonoscopy 90% (n = 103) vs. primary colonoscopy 97% (n = 71); p = 0.017], with the vast majority reporting intention to adhere in the setting of full reimbursement (97%; n = 255). Most respondents were unaware of any possible GC symptom (76%; n = 213), risk factor (73%; n = 205), and UGIE-related complication (85%; n = 237). Regular follow-up with the primary care physician (Odds Ratio (OR) 27.59, 95% confidence interval (CI) 2.99-254.57), lower perceived negative health consequences of UGIE (OR 1.40, 95% CI 1.13-1.74), and lower perceived financial burden (OR 2.46, 95% CI 1.04-5.85) were the only factors independently associated with a higher intention to undergo combined screening. CONCLUSIONS: Willingness to undergo combined endoscopic screening was notably high and positively impacted by lower perceived barriers. Additional efforts should be undertaken to improve levels of digestive health literacy.

The road to a world-unified approach to the management of patients with gastric intestinal metaplasia: a review of current guidelines.

OBJECTIVE: During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research. DESIGN: We conducted a systematic review of the literature for guidelines and consensus statements published between January 2010 and February 2023 that address the diagnosis and management of GIM. RESULTS: From 426 manuscripts identified, 16 guidelines were assessed. There was consistency across guidelines regarding the purpose of endoscopic surveillance of GIM, which is to identify prevalent neoplastic lesions and stage gastric preneoplastic conditions. The guidelines also agreed that only patients with high-risk GIM phenotypes (eg, corpus-extended GIM, OLGIM stages III/IV, incomplete GIM subtype), persistent refractory Helicobacter pylori infection or first-degree family history of gastric cancer should undergo regular-interval endoscopic surveillance. In contrast, low-risk phenotypes, which comprise most patients with GIM, do not require surveillance. Not all guidelines are aligned on histological staging systems. If surveillance is indicated, most guidelines recommend a 3-year interval, but there is some variability. All guidelines recommend H. pylori eradication as the only non-endoscopic intervention for gastric cancer prevention, while some offer additional recommendations regarding lifestyle modifications. While most guidelines allude to the importance of high-quality endoscopy for endoscopic surveillance, few detail important metrics apart from stating that a systematic gastric biopsy protocol should be followed. Notably, most guidelines comment on the role of endoscopy for gastric cancer screening and detection of gastric precancerous conditions, but with high heterogeneity, limited guidance regarding implementation, and lack of robust evidence. CONCLUSION: Despite heterogeneous populations and practices, international guidelines are generally aligned on the importance of GIM as a precancerous condition and the need for a risk-stratified approach to endoscopic surveillance, as well as H. pylori eradication when present. There is room for harmonisation of guidelines regarding (1) which populations merit index endoscopic screening for gastric cancer and GIM detection/staging; (2) objective metrics for high-quality endoscopy; (3) consensus on the need for histological staging and (4) non-endoscopic interventions for gastric cancer prevention apart from H. pylori eradication alone. Robust studies, ideally in the form of randomised trials, are needed to bridge the ample evidence gaps that exist.

MIR124-3 and NKX6-1 hypermethylation profiles accurately predict metachronous gastric lesions in a Caucasian population.

BACKGROUND: Early gastric cancer is treated endoscopically, but patients require surveillance due to the risk of metachronous gastric lesions (MGLs). Epigenetic alterations, particularly aberrant DNA methylation in genes, such as MIR124-3, MIR34b/c, NKX6-1, EMX1, MOS and CDO1, have been identified as promising biomarkers for MGL in Asian populations. We aimed to determine whether these changes could predict MGL risk in intermediate-risk Caucasian patients. METHODS: This case-cohort study included 36 patients who developed MGL matched to 48 patients without evidence of MGL in the same time frame (controls). Multiplex quantitative methylation-specific PCR was performed using DNA extracted from the normal mucosa adjacent to the primary lesion. The overall risk of progression to MGL was assessed using Kaplan-Meier and Cox proportional hazards model analyses. RESULTS: MIR124-3, MIR34b/c and NKX6-1 were successfully analyzed in 77 samples. MIR124-3 hypermethylation was detected in individuals who developed MGL (relative quantification 78.8 vs 50.5 in controls, p = 0.014), particularly in females and Helicobacter pylori-negative patients (p = 0.021 and p = 0.0079, respectively). This finding was further associated with a significantly greater risk for MGL development (aHR = 2.31, 95% CI 1.03-5.17, p = 0.042). Similarly, NKX6-1 was found to be hypermethylated in patients with synchronous lesions (relative quantification 7.9 vs 0.0 in controls, p = 0.0026). A molecular-based methylation model incorporating both genes was significantly associated with a threefold increased risk for MGL development (aHR = 3.10, 95% CI 1.07-8.95, p = 0.037). CONCLUSIONS: This preliminary study revealed an association between MIR124-3 and NKX6-1 hypermethylation and the development of MGL in a Western population. These findings may represent a burden reduction and a greener approach to patient care.

Local recurrence after endoscopic submucosal dissection of gastric neoplastic lesions: special attention should be given also to safety margins.

INTRODUCTION: The incidence of local recurrence following gastric endoscopic submucosal dissection (ESD) remains a clinical concern. We aimed to evaluate the impact of narrow safety margin (< 1 mm) on the recurrence rate. METHODS: A retrospective cohort study was conducted across two centers. Cases of R0-ESD with subsequent recurrence were compared to matched controls in a 1:2 ratio in a case-cohort analysis. RESULTS: Over a median period of 25 months (IQR 14-43), a recurrence rate of 3% (95%CI 1.7-4.3) was observed, predominantly (13/21) following R0 resections with favourable histology. Endoscopic retreatment was feasible in 18 of 21 recurrences. The proportion of R0-cases where the safety margin in both horizontal (HM) and vertical (VM) margin exceeded 1 mm was similarly distributed in the recurrence and non-recurrence group, representing nearly 20% of cases. However, cases with HM less than 1 mm, despite VM greater than 1 mm, nearly doubled in the recurrence group (7.7% vs. 3.9%), and tripled when both margins were under 1 mm (23.1% vs. 7.7%). Despite this trend, statistical significance was not achieved (p = 0.05). In the overall cohort, the only independent risk factor significantly associated with local recurrence was the presence of residual tumor at the HM (HM1) or not assessable HM (HMx) (OR 16.5 (95%CI 4.4-61.7), and OR 11.7 (95%CI 1.1-124.1), respectively). CONCLUSIONS: While not common or typically challenging to manage, recurrence post-ESD warrants attention and justifies rigorous post-procedural surveillance, especially in patients with HM1, HMx, and probably also in those with R0 resections but narrow safety margin.

Predictors of Outcomes in Gastric Neuroendocrine Tumors: A Retrospective Cohort.

Introduction/Aim: Gastric neuroendocrine tumors (GNETs) frequently have an indolent clinical course, despite their metastatic potential. The aim of the study was to identify prognostic factors associated with overall survival and risk of metastases and to evaluate the impact of serial measurements of chromogranin A (CgA). Methods: The authors performed a retrospective cohort study including consecutive patients with GNET diagnosed between 2010 and 2019, with a minimum follow-up of 1 year. Univariate and multivariate analyses were performed. Results: We included 132 patients with GNET (type I, 113 patients; type II, 1 patient; type III, 14 patients; type IV, 2 patients; not classifiable, 2 patients), with 61% being female and a mean age at diagnosis of 66 years. During the follow-up period (median 66 months), 3 (2.3%) patients died due to metastatic disease (1 patient with type III and 2 patients with type IV). Male gender (p = 0.030), type III/IV (p < 0.001), Ki-67 index >20% (p < 0.001), grade 2/3 (p < 0.001), invasion beyond the submucosa (p < 0.001), and presence of metastases (p < 0.001) were identified as risk factors for mortality in the univariate analysis. Metastasis developed in 7 patients (5.3%). Multivariable analysis revealed that Ki-67 >20% (p = 0.016) was an independent risk factor for metastasis. Overall, CgA showed a sensitivity of 20% for detection of recurrence and a specificity of 79% (sensitivity of 8% and specificity of 71% in type I GNETs). Conclusion: Identification of risk factors for the presence of metastases and for mortality in these groups of patients can help in individualizing the therapeutic strategy. CgA seems to be a weak marker for monitoring patients with GNET.

Introdução/Objetivo: Os tumores neuroendócrinos gástricos (TNEs-G) têm frequentemente um curso indolente, apesar do seu potencial metastático. O objetivo deste trabalho foi identificar fatores de prognóstico associados à sobrevida global e à metastização nos doentes com TNEs-G e avaliar o impacto da análise seriada de cromogranina A (CgA). Methods: Estudo retrospectivo incluindo doentes consecutivos admitidos por TNE-G entre 2010 e 2019, com um follow-up mínimo de 1 ano. Foi realizada análise univariada e multivariada. Results: Foram incluídos 132 doentes com TNE-G (Tipo I, 113 doentes; Tipo II, 1 doente; Tipo III, 14 doentes; Tipo IV, 2 doentes; Não classificável, 2 doentes), sendo 61% mulheres, com idade média de 66 anos. Durante o periodo de follow-up (mediana 66 meses), 3 (2.3%) doentes faleceram por doença metastática (1 doente com Tipo III e 2 com Tipo IV). O sexo masculino (p = 0,030), tipo III/IV (p < 0,001), Ki-67 index >20% (p < 0,001), Grau 2/3 (p < 0,001), invasão além da submucosa (p < 0,001) e presença de metástases (p < 0,001) foram identificados como fatores de risco para mortalidade na análise univariada. Sete doentes desenvolveram metástases (5,3%). A análise multivariáda revelou que o Ki-67 >20% (p = 0,016) era um factor de risco independente para metastização.Globalmente, a CgA mostrou uma sensibilidade de detecção de recorrência de 20% e uma especificidade de 79% (sensibilidade de 8% e especificidade de 71% em em TNEs-G do Tipo I). Conclusão: A identificação dos fatores de risco para a presença de metástases e para a mortalidade neste grupo de pacientes pode ajudar a individualizar a estratégia terapêutica. A CgA parece ser um marcador fraco para a monitorização de doentes com TNEs-G.

Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024.

1: ESGE recommends cold snare polypectomy (CSP), to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of diminutive polyps (≤ 5 mm).Strong recommendation, high quality of evidence. 2: ESGE recommends against the use of cold biopsy forceps excision because of its high rate of incomplete resection.Strong recommendation, moderate quality of evidence. 3: ESGE recommends CSP, to include a clear margin of normal tissue (1-2 mm) surrounding the polyp, for the removal of small polyps (6-9 mm).Strong recommendation, high quality of evidence. 4: ESGE recommends hot snare polypectomy for the removal of nonpedunculated adenomatous polyps of 10-19 mm in size.Strong recommendation, high quality of evidence. 5: ESGE recommends conventional (diathermy-based) endoscopic mucosal resection (EMR) for large (≥ 20 mm) nonpedunculated adenomatous polyps (LNPCPs).Strong recommendation, high quality of evidence. 6: ESGE suggests that underwater EMR can be considered an alternative to conventional hot EMR for the treatment of adenomatous LNPCPs.Weak recommendation, moderate quality of evidence. 7: Endoscopic submucosal dissection (ESD) may also be suggested as an alternative for removal of LNPCPs of ≥ 20 mm in selected cases and in high-volume centers.Weak recommendation, low quality evidence. 8: ESGE recommends that, after piecemeal EMR of LNPCPs by hot snare, the resection margins should be treated by thermal ablation using snare-tip soft coagulation to prevent adenoma recurrence.Strong recommendation, high quality of evidence. 9: ESGE recommends (piecemeal) cold snare polypectomy or cold EMR for SSLs of all sizes without suspected dysplasia.Strong recommendation, moderate quality of evidence. 10: ESGE recommends prophylactic endoscopic clip closure of the mucosal defect after EMR of LNPCPs in the right colon to reduce to reduce the risk of delayed bleeding.Strong recommendation, high quality of evidence. 11: ESGE recommends that en bloc resection techniques, such as en bloc EMR, ESD, endoscopic intermuscular dissection, endoscopic full-thickness resection, or surgery should be the techniques of choice in cases with suspected superficial invasive carcinoma, which otherwise cannot be removed en bloc by standard polypectomy or EMR.Strong recommendation, moderate quality of evidence.

Curative criteria for endoscopic treatment of gastric cancer.

Endoscopic treatment, particularly endoscopic submucosal dissection, has become the primary treatment for early gastric cancer. A comprehensive optical assessment, including white light endoscopy, image-enhanced endoscopy, and magnification, are the cornerstones for clinical staging and determining the resectability of lesions. This paper discusses factors that influence the indication for endoscopic resection and the likelihood of achieving a curative resection. Our review stresses the critical need for interpreting the histopathological report in accordance with clinical guidelines and the imperative of tailoring decisions based on the patients' and lesions' characteristics and preferences. Moreover, we offer guidance on managing complex scenarios, such as those involving non-curative resection. Finally, we identify future research avenues, including the role of artificial intelligence in estimating the depth of invasion and the urgent need to refine predictive scores for lymph node metastasis and metachronous lesions.

Management of high risk T1 gastric adenocarcinoma following endoscopic resection.

Endoscopic submucosal dissection has revolutionized the treatment of early gastric cancer. However, cases that do not meet the curability criteria have a higher risk of lymph node metastasis and salvage surgery is still considered the next treatment approach to increase the chance of cure. Nevertheless, not all high-risk resections entail the same level of risk, emphasizing the utmost importance of individualized stratification for further treatment. In this review, we aim to examine the current evidence concerning the management following a high-risk non-curative resection, highlighting the existing approaches, while also presenting upcoming strategies that attempt to improve patient outcomes, minimize adverse events, and provide a tailored management.

Western outcomes of circumferential endoscopic submucosal dissection for early esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Circumferential endoscopic submucosal dissection (cESD) in the esophagus has been reported to be feasible in small Eastern case series. We assessed the outcomes of cESD in the treatment of early esophageal squamous cell carcinoma (ESCC) in Western countries. METHODS: We conducted an international study at 25 referral centers in Europe and Australia using prospective databases. We included all patients with ESCC treated with cESD before November 2022. Our main outcomes were curative resection according to European guidelines and adverse events. RESULTS: A total of 171 cESDs were performed on 165 patients. En bloc and R0 resections rates were 98.2% (95% confidence interval [CI], 95.0-99.4) and 69.6% (95% CI, 62.3-76.0), respectively. Curative resection was achieved in 49.1% (95% CI, 41.7-56.6) of the lesions. The most common reason for noncurative resection was deep submucosal invasion (21.6%). The risk of stricture requiring 6 or more dilations or additional techniques (incisional therapy/stent) was high (71%), despite the use of prophylactic measures in 93% of the procedures. The rates of intraprocedural perforation, delayed bleeding, and adverse cardiorespiratory events were 4.1%, 0.6%, and 4.7%, respectively. Two patients died (1.2%) of a cESD-related adverse event. Overall and disease-free survival rates at 2 years were 91% and 79%. CONCLUSIONS: In Western referral centers, cESD for ESCC is curative in approximately half of the lesions. It can be considered a feasible treatment in selected patients. Our results suggest the need to improve patient selection and to develop more effective therapies to prevent esophageal strictures.

Development and validation of the PERCEPT-PREVENT tool to determine risk perception and attitudes towards digestive cancer screening.

BACKGROUND AND AIMS: Colorectal cancer (CRC) screening is recommended worldwide, while gastric cancer (GC) screening may also be defendable in some settings. However, adherence rates and factors influencing participation are not well characterized. This study aimed to validate a tool to determine risk perception of CRC and GC and also of endoscopy-related complications. METHODS: A questionnaire in CRC risk perception based on the Health Belief Model was used. Forward/backward translation (English-Portuguese) and cultural adaptation were performed. After revision by a panel of experts, the questionnaire was adapted to target GC risk perception and perceptions towards endoscopy-related complications. The final version of the questionnaire (PERCEPT-PREVENT tool) was applied to 44 individuals, through telephonic interview, at enrolment and at intervals ≤3 weeks. Test-retest reliability and agreement were assessed. RESULTS: Almost perfect reliability between test and retest was obtained for CRC symptom knowledge score (ICC = 0.88), risk factor knowledge score (ICC = 0.89), and perceived severity (ICC = 0.84). At least moderate agreement between test and retest was obtained for GC symptom knowledge score (ICC = 0.94), risk factor knowledge score (ICC = 0.92), and perceived severity (ICC = 0.58). Test-retest reliability was assessed for barrier domains [faecal occult blood test ICC = 0.63; colonoscopy ICC = 0.79; upper GI endoscopy (UGIE) ICC = 0.83]. A total of 91% and 98% of participants gave the same answer in the test and retest for preferred method of CRC screening and intention to undergo UGIE for GC screening combined with a screening colonoscopy, respectively. DISCUSSION: PERCEPT-PREVENT is a valid and reliable tool for CRC and GC risk perception evaluation.

Combined gastric and colorectal cancer endoscopic screening may be cost-effective in Europe with the implementation of artificial intelligence: an economic evaluation.

BACKGROUND/AIMS: Endoscopic screening for gastric cancer (GC) is not recommended in low-intermediate incidence countries. Artificial intelligence (AI) has high accuracy in GC detection and might increase the cost-effectiveness of screening strategies. We aimed to assess the cost-effectiveness of AI for GC detection in settings with different GC incidence and different accuracies of AI systems. METHODS: Cost-effectiveness analysis (using Markov model) comparing different screening strategies (no screening versus single esophagogastroduodenoscopy (EGD) at 50 years versus stand-alone EGD every 5/10 years versus combined EGD and screening colonoscopy once or twice per decade in Netherlands, Italy and Portugal) with variable AI accuracy settings. The primary outcome was the incremental cost-effectiveness ratio of the different strategies versus no screening. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Without AI, one single EGD at 50 years (Netherlands, Italy, Portugal), EGD combined with screening colonoscopy once per decade (Italy and Portugal) and EGD combined with screening colonoscopy twice per decade (Portugal) are cost-effective when compared with no screening. If AI increases the accuracy of EGD by at least 1% in comparison to the accuracy of white-light endoscopy accuracy (89%), combined screening twice per decade also becomes cost-effective in Italy. If AI accuracy reaches at least 96%, combined screening once per decade is also cost-effective in the Netherlands. DISCUSSION: In European countries, AI-assisted EGD may improve the cost-effectiveness of GC screening with combined EGD and screening colonoscopy. The actual effect of AI on cost-effectiveness may vary dependent on the accuracy and costs of the AI system.

Diagnostic Performance of Deep Learning Models for Gastric Intestinal Metaplasia Detection in Narrow-band Images.

Gastric Intestinal Metaplasia (GIM) is one of the precancerous conditions in the gastric carcinogenesis cascade and its optical diagnosis during endoscopic screening is challenging even for seasoned endoscopists. Several solutions leveraging pre-trained deep neural networks (DNNs) have been recently proposed in order to assist human diagnosis. In this paper, we present a comparative study of these architectures in a new dataset containing GIM and non-GIM Narrow-band imaging still frames. We find that the surveyed DNNs perform remarkably well on average, but still measure sizeable inter-fold variability during cross-validation. An additional ad-hoc analysis suggests that these baseline architectures may not perform equally well at all scales when diagnosing GIM.Clinical relevance- Enhanching a clinician's ability to detect and localize intestinal metaplasia can be a crucial tool for gastric cancer management policies.

Predicting residual neoplasia after a non-curative gastric ESD: validation and modification of the eCura system in the Western setting: the W-eCura score.

OBJECTIVE: To evaluate the risk factors for lymph node metastasis (LNM) after a non-curative (NC) gastric endoscopic submucosal dissection (ESD) and to validate and eventually refine the eCura scoring system in the Western setting. Also, to assess the rate and risk factors for parietal residual disease. DESIGN: Retrospective multicentre multinational study of prospectively collected registries from 19 Western centres. Patients who had been submitted to surgery or had at least one follow-up endoscopy were included. The eCura system was applied to assess its accuracy in the Western setting, and a modified version was created according to the results (W-eCura score). The discriminative capacities of the eCura and W-eCura scores to predict LNM were assessed and compared. RESULTS: A total of 314 NC gastric ESDs were analysed (72% high-risk resection (HRR); 28% local-risk resection). Among HRR patients submitted to surgery, 25% had parietal disease and 15% had LNM in the surgical specimen. The risk of LNM was significantly different across the eCura groups (areas under the receiver operating characteristic curve (AUC-ROC) of 0.900 (95% CI 0.852 to 0.949)). The AUC-ROC of the W-eCura for LNM (0.916, 95% CI 0.870 to 0.961; p=0.012) was significantly higher compared with the original eCura. Positive vertical margin, lymphatic invasion and younger age were associated with a higher risk of parietal residual lesion in the surgical specimen. CONCLUSION: The eCura scoring system may be applied in Western countries to stratify the risk of LNM after a gastric HRR. A new score is proposed that may further decrease the number of unnecessary surgeries.

Gastric Cancer: A Practical Review on Management of Individuals with Hereditary or Familial Risk for Gastric Cancer.

Gastric adenocarcinoma is one of the most frequent and deadly cancers worldwide. However, its incidence is variable, being higher in eastern countries where screening the general population is recommended. On the other hand, in low to intermediate-risk countries, screening the general population may not be cost-effective, and therefore, it is necessary to be aware of high-risk populations that may benefit from adequate screening and surveillance. It is not always easy to identify these individuals, leading to a late diagnosis of gastric adenocarcinoma. In this review, the authors intend to summarize the data required to identify the population at risk of sporadic or familial gastric adenocarcinoma and the beginning of screening and its surveillance, with the final aim of increasing early detection of gastric adenocarcinoma and decreasing morbimortality. The authors highlight the importance to be aware of the several hereditary syndromes and MAPS recommendations and apply screen and surveillance protocols. The high-risk syndromes to gastric adenocarcinoma are gastric adenocarcinoma and proximal polyposis of the stomach, hereditary diffuse gastric cancer, and familial intestinal gastric cancer.

O adenocarcinoma gástrico é um dos cancros mais frequentes e mortais em todo o mundo. No entanto, a sua incidência é variável, sendo maior nos países orientais, onde o rastreio da população geral está recomendado. Por outro lado, nos países de risco baixo a intermediário, o rastreio da população geral pode não ser custo-efetivo e, portanto, é necessário conhecer quais são as populações de alto risco que podem beneficiar de rastreio e vigilância adequados. Porém, nem sempre é fácil identificar esses indivíduos levando a um diagnóstico tardio de adenocarcinoma gástrico. Nesta revisão, os autores pretendem resumir a informação necessária à identificação da população em risco de adenocarcinoma gástrico esporádico ou familiar e o início do rastreio e sua vigilância, com o objetivo final de otimizar a deteção precoce do adenocarcinoma gástrico e diminuir a morbimortalidade. Os autores salientam a importância de conhecer as diversas síndromes hereditárias e recomendações MAPS e aplicar protocolos de rastreio e vigilância. As síndromes de maior risco para adenocarcinoma gástrico são GAPPS, HDGC e FIGC.