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Open research questions in Gastric Cancer Management and Outcomes

38 unresolved questions extracted from the limitations and future-work sections of 303 Gastric Cancer Management and Outcomes papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • 10) metastasis, the oncologic benefit of splenectomy remains controversial, while its association with increased postoperative morbidity is well established.

    Redefining the Role of Splenectomy in Scirrhous Gastric Cancer: Toward a Selective Multimodal Strategy · 2026 · DOI

  • Several limitations should be acknowledged. First, only firstline, phase III randomized trials were analyzed, which may limit generalizability to later-line settings; however, this approach ensures inclusion of the highest-quality evidence with standardized treatment protocols and survival endpoints. Second, this metaanalysis relied on aggregate, study-level data, precluding patientlevel adjustment for confounders such as performance status, tumor burden, or subsequent therapies. Nonetheless, trial-level stratification and sensitivity analyses help mitigate these effects and strengthen the internal validity of pooled results.

    Impact of metastatic pattern and histologic subtype on PD-(L)1 inhibitor efficacy in HER2-negative advanced gastric and gastroesophageal cancer: a meta-analysis · 2026 · DOI

  • Future research should focus on integrating spatial and single- cell immune profiling to elucidate mechanisms of resistance to immune checkpoint inhibition in peritoneal and diffuse-type dis- ease. Evaluating mechanism-driven combination regimens, includ- ing PD-(L)1 inhibitors paired with anti-fibrotic, anti-VEGF, or anti- TGF-b agents, as well as locoregional therapies like HIPEC or PIPAC may help remodel immune-TME and enhance therapeutic response. Several of these strategies are currently under investiga- tion in preclinical models or early-phase trials in GC, including intraperitoneal chemotherapy combined with immune checkpoint inhibitor (22–24, 27). In parallel, prospective, biomarker-driven clinical trials stratified by histologic subtype and metastatic pattern are warranted to validate subgroup-specific therapeutic strategies. Finally, the incorporation of immune gene expression signatures could enable real-time monitoring of treatment response and resistance evolution.

    Impact of metastatic pattern and histologic subtype on PD-(L)1 inhibitor efficacy in HER2-negative advanced gastric and gastroesophageal cancer: a meta-analysis · 2026 · DOI

  • Although various risk factors for delayed post-polypectomy bleeding (DPPB) have been identified, the relationship between immediate post-polypectomy bleeding (IPPB) and subsequent DPPB risk remains unclear.

    Immediate post-polypectomy bleeding is associated with an increased risk of delayed post-polypectomy bleeding: A large retrospective cohort study · 2026 · DOI

  • Moreover, the long-term prognosis following pulley traction-assisted ESD with dental floss has not yet been systematically evaluated, and relevant data remain insufficient. , 3–5 years) are lacking, limiting a comprehensive evaluation the long-term effects of pulley traction-assisted ESD with of dental floss on recurrence control and survival outcomes. To enhance the reliability and generalizability of the findings, future multicenter, large-sample prospective studies are warranted.

    Endoscopic submucosal dissection for early gastric cancer: A review of comparative perspectives on treatment outcomes <i>vs</i> gastrectomy · 2026 · DOI

  • BackgroundGastric cancer management is heterogeneous, and although the treating surgeon leads decisions across the pathway, surgeon-level outcome variation remains poorly quantified.

    The Surgical Assessment and Healthcare (SAH) Index: A Risk-Adjusted Framework for Surgeon-Level Quality Audit in Gastric Cancer · 2026 · DOI

  • PURPOSE: Esophagojejunostomy (EJ) stricture is a clinically significant complication following proximal and total gastrectomy, yet the underlying factors contributing to its development and its long-term implications remain poorly defined.

    Factors associated with esophagojejunostomy stricture and its clinical impact after gastrectomy: a 10-year single-center study · 2026 · DOI

  • BACKGROUND Currently, there is no consensus on whether proximal gastrectomy (PG) or total gastrectomy (TG) should be used for upper gastric signet-ring cell carcinoma (SRCC), and the long-term oncological outcome and postoperative nutritional status is still debatable.

    Prognosis of signet-ring cell carcinoma after proximal gastrectomy was comparable to total gastrectomy but with better nutrition status · 2026 · DOI

  • Background: The clinical significance of lymphatic invasion in mucosal early gastric cancer (EGC) treated with endoscopic submucosal dissection (ESD) remains unclear.

    Long-Term Outcomes of Mucosal Early Gastric Cancer with Lymphatic Invasion as the Sole Non-Curative Factor After Endoscopic Submucosal Dissection · 2026 · DOI

  • ≥65 years and women aged ≥75 years. Therefore, GC screening will likely not be recommended for men and women in their 40s and early 50s, even by 2035 [51]. In contrast, in the US, comprehensive GC screening is rec- ommended for high-risk groups, particularly immigrants from countries with high incidence rates of GC. Screening should focus on individuals with risk factors such as H. pylori infection, family history, and gastric atrophy/IM [52]. Policymakers should also consider offering these screenings to high-risk populations, even in the absence of symptoms. Many Western countries that accept large numbers of immigrants from high-incidence countries could benefit from such studies. In Japan, there is a need to consider new approaches for the screening of high-risk groups.

    Laparoscopy-assisted gastrectomy remains safe and feasible for gastric cancer patients with a history of upper abdominal surgery · 2026 · DOI

  • Chika Kusano1 Fumiaki Ishibashi2 Chikamasa Ichita3 Takuji Gotoda4 1Department of Medicine, Division of Gastroenterology and Hepatology, Kitasato University School of Medicine, Sagamihara, Japan 2Department of Gastroenterology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan 3Gastroenterology Medicine Center, Shonan Kamakura General Hospital, Kamakura, Japan 4Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan Correspondence: Chika Kusano ([email protected]) Received: 31 March 2025 Revised: 11 May 2025 Accepted: 13 May 2025 Funding: This study was supported by the Ministry of Health, Labor and Welfare of Japan (Grant Number 24EA1001). Keywords: endoscopy | gastric cancer screening | Helicobacter pylori test | serum pepsinogen test | upper gastrointestinal contrast radiography ABSTRACT Gastric cancer (GC) remains a major global health concern, particularly in East Asia, Central Asia, and Eastern Europe, where its incidence and mortality rates are high. Helicobacter pylori infection is the primary cause of GC and leads to carcinogenic progression from nonatrophic gastritis to cancer. Although screening programs have been implemented in high-risk countries, such as Japan and South Korea, comprehensive strategies remain limited globally. This study reviewed the status of GC screening worldwide and prevention strategies in regions with different risks. Various GC screening methods have been developed, including H. pylori serology, serum pepsinogen testing, upper gastrointestinal contrast radiography, and endoscopy. Endoscopic screening has shown superior sensitivity and specificity, reducing GC mortality by up to 47% in South Korea and demonstrating higher detection rates than upper gastrointestinal contrast radiography and pepsinogen testing. However, cost-effectiveness remains a challenge, particularly in Western countries where the overall GC prevalence is lower. Risk stratification using a combination of H. pylori serology and pepsinogen testing has been adopted in Japan to optimize screening efficiency. Additionally, H. pylori eradication has been recognized as a cost-effective strategy to reduce the incidence of GC with economic benefits demonstrated in Japan and other high-risk regions. In the United States, targeted screening of high-risk immigrant populations has been suggested to enhance cost-effectiveness. GC screening strategies should consider developing epidemiological trends, cost-effectiveness, and risk-based approaches. Future efforts should focus on expanding targeted screening initiatives to high-risk groups to improve early detection and survival rates.

    Laparoscopy-assisted gastrectomy remains safe and feasible for gastric cancer patients with a history of upper abdominal surgery · 2026 · DOI

  • Esophageal VCE has its limitations due to its impossibility to perform a biopsy or other necessary procedures in Barret’s esophagus. Moreover, for an accurate diagnose of EV and for a correct grading of EV, air insufflation is also not possible by using VCE instead of endoscopic maneuvers. COLON CAPSULE ENDOSCOPY Colon Capsule Endoscopy (CCE) is defined as a new promising modality for colon evaluation. Its advantage relates to the noninvasiveness of the procedure, compared to conventional colonoscopy, which some patients may regard as an unpleasant experience. Since the first M2A small bowel capsule was launched in 2000, great interests have led to the development of the first capsule for the colon. The PillCam COLON is available since 2006, followed by its successor the PillCam COLON2 in 2009. This CCE contains 2 cameras on both sides, with viewing angles wider (up to 172º), creating the possibility of an approximate 360º image of the colon wall. During active movement, it can capture up to 35 frames per second [19].

    Mo1192 A CHANGING MAP OF GASTRIC CANCER IN THE UNITED STATES: 20- YEAR TRENDS REVEAL PERSISTENT AND EMERGING HIGH-RISK REGIONS · 2026 · DOI

  • EUS imaging is useful not only for detection and characterization of small pNETs, but also for precise localization during laparoscopic/robotic surgery by performing EUS-guided tattooing preoperatively, using either sterile India ink or indocyanine green [12]. Although surgery is the mainstay for pNETs, other locally ablative therapies like EUS-guided radiofrequency ablation (EUS-RFA) have been described in a limited number of cases (N=61 patients with 73 tumors with the mean size of 16 mm, one third insulinomas) [13]. The overall effectiveness of 96%, for functional and non-functional pNETs, as well as the mild adverse events (13.7%) indicates the method might be reasonable for small pNETs, especially for patients unfit for surgery. Gastro-Entero-Pancreatic Neuroendocrine Tumors What is New in Gastroenterology and Hepatology 65 Targeting somatostatin receptors with similar agents for both imaging and therapy paved the way to theranostic applications and molecular targeting of these exotic tumors. Other studies targeted the C-X-C motif chemokine receptor 4 (CXCR4), because it is overexpressed in high-grade GEP-NETs and can be used as a therapeutic target, even in somatostatin receptor negative NETs. Other receptors are also targeted: glucagon-like peptide-1 (GLP-1) receptor for insulinoma, cholecystokinin 2 receptor (CCK2R) for gastric and pancreatic NETs, etc. [14]. Various other targeted radionuclides are currently assessed for both diagnosis and therapy (11Carbon, 212Lead, 177Lutetium, using innovative approaches: targeting with antagonists instead of agonists, alpha instead of beta particles, intra-arterial versus intravenous administration, combination therapy, etc. [14]. 55Cobalt, etc.), 166Holmium, 212Bismuth, 64Copper, 90Ytrium, gastro-entero-pancreatic neuroendocrine tumors, not being very frequent, are quite difficult lesions, but new developments in the diagnosis and management of these diseases give hope for a better therapeutic approach. CONSENT FOR PUBLICATION Not applicable. CONFLICT OF INTEREST The author confirms that this chapter contents have no conflict of interest. ACKNOWLEDGEMENTS Declared none. REFERENCES [1] Pavel M, Öberg K, Falconi M, et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020; 31(7): 844-60. [http://dx.doi.org/10.1016/j.annonc.2020.03.304] [PMID: 32272208] [2] Ramage JK, Ahmed A, Ardill J, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut 2012; 61(1): 6-32. [http://dx.doi.org/10.1136/gutjnl-2011-300831] [PMID: 22052063] [3] Ma ZY, Gong YF, Zhuang HK, et al. Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management. World J Gastroenterol 2020; 26(19): 2305-22. [http://dx.doi.org/10.3748/wjg.v26.i19.2305] [PMID: 32476795] [4] [5] Amin MB, Edge S, Greene F, Eds. AJCC Cancer Staging Manual. 2017. [http://dx.doi.org/10.1007/978-3-319-40618-3] Kunz PL, Reidy-Lagunes D, Anthony LB, et al. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas 2013; 42(4): 557-77. [http://dx.doi.org/10.1097/MPA.0b013e31828e34a4] [PMID: 23591432] 66 What is New in Gastroenterology and Hepatology Săftoiu and Constantinescu [6] [7] [8] [9] Zhang MY, He D, Zhang S. Pancreatic neuroendocrine tumors G3 and pancreatic neuroendocrine carcinomas: Differences in basic biology and treatment. World J Gastrointest Oncol 2020; 12(7): 705- 18. [http://dx.doi.org/10.4251/wjgo.v12.i7.705] [PMID: 32864039] Shah MH, Goldner WS, Halfdanarson TR, et al. NCCN Guidelines Insights: Neuroendocrine and Adrenal Tumors, Version 2.2018. J Natl Compr Canc Netw 2018; 16(6): 693-702. [http://dx.doi.org/10.6004/jnccn.2018.0056] [PMID: 29891520] Ito T, Jensen RT. Molecular imaging in neuroendocrine tumors: recent advances, controversies, unresolved issues, and roles in management. Curr Opin Endocrinol Diabetes Obes 2017; 24(1): 15-24. [PMID: 27875420] I, Grozinsky-Glasberg S.

    Mo1192 A CHANGING MAP OF GASTRIC CANCER IN THE UNITED STATES: 20- YEAR TRENDS REVEAL PERSISTENT AND EMERGING HIGH-RISK REGIONS · 2026 · DOI

  • An important limitation of this review is the potential for selection bias and confounding by indication because ESD was more frequently used for larger, more complex, and histologically advanced lesions, whereas EMR was generally applied to smaller and lower-risk lesions.

    A Systematic Review Showing the Comparative Efficacy and Safety of Endoscopic Submucosal Dissection Versus Endoscopic Mucosal Resection in the Management of Colorectal Neoplasia · 2026 · DOI

  • Future research should focus on prospective multicenter studies to validate our findings and further explore the role of H-ESD in specific lesion types. Additionally, strategies for mitigating the impact of intraprocedural AEs, such as novel traction devices and advanced hemostatic techniques, should be investigated.

    Endoscopic Submucosal Dissection for Colorectal Lesions in a Community-based European Hospital: Experience and Learning Curve · 2026 · DOI

  • The patients were divided into groups taking into account the revealed structural changes in the gastric mucosa: group I— 7 people with gastric mucosal atrophy without intestinal metaplasia (IM); group II— 16 individuals with gastric mucosal atrophy with IM limited by the antrum; group III— 45 people with diffuse IM against the background of gastric mucosal atrophy; group IV— 10 individuals with gastric mucosal dysplasia.

    Features of cytokine balance with the progression of structural changes in the gastric mucosa in patients with atrophic gastritis · 2021 · DOI

  • Surgical treatment is rarely performed in metastatic disease due to lack of evidence of increased survival time; randomized prospective studies such as the Renaissance / FLOT 5 You may cite this article as: Omari J, Drewes R, Othmer M, Hass P, Pech M, Powerski M.

    Treatment of metastatic gastric adenocarcinoma with image-guided high-dose rate, interstitial brachytherapy as second-line or salvage therapy · 2019 · DOI

  • Emerging evidence suggests that dynamic changes in tumor marker levels may better reflect tumor burden and biological behavior than static measurements, yet systematic evaluation of different dynamic patterns remains lacking.

    Dynamic monitoring of serum tumor markers in predicting recurrence after radical gastrectomy for gastric cancer · 2026 · DOI

  • Importance: Evidence of implementation of laparoscopic gastrectomy for locally advanced gastric cancer is currently insufficient, as the primary end point in previous prospective studies was evaluated at a median follow-up time of 3 years.

    Five-Year Survival Outcomes of Laparoscopy-Assisted vs Open Distal Gastrectomy for Advanced Gastric Cancer · 2023 · DOI

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38 open questions have been extracted from the limitations and future-work passages of 303 Gastric Cancer Management and Outcomes papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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