Background: Clarithromycin (CAM) resistance is a major contributor to the failure to eradicate Helicobacter pylori (H. pylori). The mixed-infection ratio of CAM-susceptible and CAM-resistant H. pylori strains differs among individuals. Pyrosequencing analysis can be used to quantify gene mutations at position each 2142 and 2143 of the H. pylori 23S rRNA gene in intragastric fluid samples. Herein, we aimed to clarify the impact of the rate of mixed infection with CAM-susceptible and CAM-resistant H. pylori strains on the success rate of CAM-containing eradication therapy. Materials and methods: Sixty-four H. pylori-positive participants who received CAM-based eradication therapy, also comprising vonoprazan and amoxicillin, were enrolled in this prospective cohort study. Biopsy and intragastric fluid samples were collected during esophagogastroduodenoscopy. H. pylori culture and CAM-susceptibility tests were performed on the biopsy samples, and real-time PCR and pyrosequencing analyses were performed on the intragastric fluid samples. The mutation rates and eradication success rates were compared. Results: The overall CAM-based eradication success rate was 84% (54/64): 62% (13/21) for CAM-resistant strains, and 95% (39/41) for CAM-sensitive strains. When the mutation rate of the 23S rRNA gene was 20% or lower for both positions (2142 and 2143), the eradication success rate was 90% or more. However, when the mutation rate was 20% or higher, the eradication success rate was lower (60%). Conclusions: The mutation rate of the CAM-resistance gene was related to the success of eradication therapy, as determined via pyrosequencing analysis.

Panel-based comprehensive genomic profiling is used in clinical practice worldwide; however, large real-world datasets of patients with advanced gastric cancer are not well known. We investigated what differences exist in clinically relevant alterations for molecularly defined or age-stratified subgroups. This was a collaborative biomarker study of a real-world dataset from comprehensive genomic profiling testing (Foundation Medicine, Inc.). Hybrid capture was carried out on at least 324 cancer-related genes and select introns from 31 genes frequently rearranged in cancer. Overall, 4634 patients were available for analyses and were stratified by age (≥ 40/< 40 years), microsatellite instability status, tumor mutational burden status (high 10 ≥ /low < 10 Muts/Mb), Epstein–Barr virus status, and select gene alterations. We analyzed the frequency of alterations with a chi-square test with Yate’s correction. Genes with frequent alterations included TP53 (60.1

PURPOSE Panel-based comprehensive genomic profiling (CGP) is used in clinical practice worldwide; however, large real-world data (RWD) of patients with advanced small intestine cancer have not been characterized. We investigated differences in the prevalence of clinically relevant alterations across molecularly defined or age-stratified subgroups. PATIENTS AND METHODS This was a collaborative biomarker study of RWD from CGP testing (Foundation Medicine, Inc). Hybrid capture was conducted on at least 324 cancer-related genes and select introns from up to 31 genes frequently rearranged in cancer. Overall, 1,364 patients with advanced small intestine cancer were available for analyses and were stratified by age (≥40 years/<40 years), microsatellite instability (MSI) status, tumor mutational burden (TMB) status (high ≥10/low <10 Muts/Mb), and select gene alterations. The frequency of alterations was analyzed using a chi-square test with Yate's correction. RESULTS Genes with frequent alterations included TP53 (59.8%), KRAS (54.8%), APC (27.7%), and CDKN2A (22.4%). Frequent genes with amplifications were MYC (6.7%), MDM2 (5.9%), GATA6 (5.5%), and CCND1 (3.4%). Patients younger than 40 years had significantly lower frequency of APC mutations than those 40 years and older (10.4% v 28.7%; P = .0008). Druggable genomic alterations were detected in 22.3% of patients: BRAF V600E (1.2%), BRCA1 (1.8%), BRCA2 (3.2%), ERBB2 amplification (3.2%), KRAS G12C (3.3%), NTRK1/2/3 fusion (0.07%), MSI-high (7.0%), and TMB-high (12.2%), with no significant differences in the frequency according to age (<40 years v ≥40 years; 22.1% v 22.3%). TMB of 10-20 Mut/Mb was observed in 4.8% of patients, and TMB ≥20 Mut/Mb was seen in 7.3% of the cohort. CONCLUSION RWD from clinical panel testing revealed the genomic landscape in small intestine cancer by subgroup. These findings provide insights for the future development of treatments in advanced small intestine cancer.

Messenger ribonucleic acid (mRNA) vaccination against coronavirus disease 2019 (COVID-19) is an effective prevention strategy, despite a limited understanding of the molecular mechanisms underlying the host immune system and individual heterogeneity of the variable effects of mRNA vaccination. We assessed the time-series changes in the comprehensive gene expression profiles of 200 vaccinated healthcare workers by performing bulk transcriptome and bioinformatics analyses, including dimensionality reduction utilizing the uniform manifold approximation and projection (UMAP) technique. For these analyses, blood samples, including peripheral blood mononuclear cells (PBMCs), were collected from 214 vaccine recipients before vaccination (T1) and on Days 22 (T2, after second dose), 90, 180 (T3, before a booster dose), and 360 (T4, after a booster dose) after receiving the first dose of BNT162b2 vaccine (UMIN000043851). UMAP successfully visualized the main cluster of gene expression at each time point in PBMC samples (T1-T4). Through differentially expressed gene (DEG) analysis, we identified genes that showed fluctuating expression levels and gradual increases in expression levels from T1 to T4, as well as genes with increased expression levels at T4 alone. We also succeeded in dividing these cases into five types based on the changes in gene expression levels. High-throughput and temporal bulk RNA-based transcriptome analysis is a useful approach for inclusive, diverse, and cost-effective large-scale clinical studies.

642 Background: Panel-based comprehensive genomic profiling (CGP) is used in clinical practice worldwide, however, large aggregated RWD of patients with advanced small intestine cancer have not been characterized. In particular, there has been limited data regarding examining CGP in pediatric/ Adolescent and Young Adult (AYA) small intestine cancer. For patient subgroups, it is unclear what clinically relevant alterations co-occur. Here, we investigated the genomic landscape of small intestine cancer patients, stratified by sub-group to help refine and discover new targets for improved cancer therapies in advanced small intestine cancer. Methods: This is a collaborative biomarker study using RWD paired with CGP testing (Foundation Medicine, Inc.). Hybrid capture was carried out on up to 395 cancer-related genes and select introns from up to 31 genes frequently rearranged in cancer. One thousand three hundred sixty-four patients were available for analyses and were stratified by age (≥40/ < 40), MSI status, tumor mutational burden (TMB) status (High ≥10/Low < 10Muts/Mb), and select gene alterations. Using a chi-square test with Yate’s correction, frequencies of alterations were analyzed according to clinical or genomic background. Results: Genes with frequent alterations including mutation, amplification, and rearrangement/fusion were TP53 (59.8%), KRAS (54.8%), APC (27.7%), CDKN2A (22.4%), and SMAD4 (20.2%). Genomic profiling according to age, MSI, and TMB status is shown in the following table. In pediatric/AYA patients, frequency of APC alterations was significantly low ( P< 0.001). In KRAS mutated tumors, codon 12 most abundant mutations were G12D (31.1%) followed by G12V (22.3%), G12C (6.2%), and G12R (5.1%), while G13D (13.8%) was the predominant mutation in codon 13. In TMB-High tumors, which were detected in 12% of patients, the mutation rate of KRAS was modestly lower compared to TMB-Low tumors (42.3% vs. 53.3%). Frequent genes with amplification were MYC (6.7%), MDM2 (5.9%), GATA6 (5.5%), CCND1 (3.4%), FGF19 (3.3%), and ERBB2 (2.3%). The number of any gene amplification was lower in MSI-High compared to TMB-High population. Conclusions: RWD from clinical panel testing revealed the genomic landscape in small intestine cancer and differences in CGP according to clinical or genomic background. These findings would provide insight on the direction of the future development of the treatment in advanced small intestine cancer.[Table: see text]

Although there are many Helicobacter pylori (H. pylori) diagnostic methods, the culture and antibiotic susceptibility test is an important method for selecting the most effective H. pylori eradication regimen. However, this diagnostic method is complicated and takes several days; therefore, the development of a rapid and simple diagnostic method is required. Eradication failure due to clarithromycin (CAM) resistance should also be considered. In this study, we report the clinical evaluation of point‐of‐care testing (POCT) kit using intragastric fluid, a novel kit for detecting H. pylori and CAM resistance.

Background A persistently high methylation level in gastric mucosa after Helicobacter pylori ( H. pylori ) eradication is presumed to be a risk for metachronous gastric cancer (MGC); however, long-term changes in aberrant DNA methylation and histological gastritis have been unclear. Our aim was to examine changes in DNA methylation and histological gastritis according to the occurrence of MGC. Methods Subjects were classified into 3 groups: 25 patients in whom metachronous gastric cancers occurred after the initial endoscopic resection (ER) for early gastric cancer and H. pylori eradication (MGC group), 17 patients in whom MGC did not occur for more than 5 years after initial ER and H. pylori eradication (non-MGC group) and 29 patients without a history of gastric cancer who succeeded in eradication more than 5 years ago (HP group). Aberrance of DNA methylation in 3 genes (miR-124a-3, EMX1, NKX6-1) and histological score of atrophy and intestinal metaplasia (IM) were evaluated using biopsy samples before and more than a mean of 5 years after H. pylori eradication. Results The methylation level of miR-124a-3 in the HP group and non-MGC group and that of EMX1 in the HP group significantly decreased in the long term after eradication. In the MGC group, H. pylori eradication did not improve aberrant methylation, and the Z-score significantly increased. There were significant positive correlations between methylation levels in miR-124a-3 and EMX1 and histological findings after eradication. Conclusions A persistently high methylation level after H. pylori eradication reflected precancerous mucosal conditions and led to long-term MGC.

Introduction Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic even after vaccination. We aimed to identify immunological heterogeneity over time in vaccinated healthcare workers using neutralization antibodies and neutralizing activity tests. Methods Serum samples were collected from 214 healthcare workers before vaccination (pre) and on days 22, 90, and 180 after receiving the first dose of BNT162b2 vaccine (day 0). Neutralization antibody (NAb, SARS-CoV-2 S-RBD IgM/IgG) titers and two kinds of surrogate virus neutralization tests (sVNTs) were analyzed (UMIN000043851). Results The NAb (SARS-CoV-2 S-RBD IgG) titer peaked on day 90 after vaccination (30,808.0 mu g/ml +/- 35,211; p < 0.0001) and declined on day 180 (11,678.0 mu g/ml +/- 33,770.0; p < 0.0001). The neutralizing activity also peaked on day 90 and declined with larger individual differences than those of IgG titer on day 180 (88.9% +/- 15.0%, 64.8% +/- 23.7%, p < 0.0001). We also found that the results of POCT-sVNT (immunochromatography) were highly correlated with those of conventional sVNT (ELISA). Conclusions Neutralizing activity is the gold standard for vaccine efficacy evaluation. Our results using conventional sVNT showed large individual differences in neutralizing activity reduction on day 180 (64.8% +/- 23.7%), suggesting an association with the difference in vaccine efficacy. POCT-sVNT is rapid and user-friendly; it might be used for triage in homes, isolation facilities, and event venues without restrictions on the medical testing environment.

It is widely accepted that hepatitis B virus (HBV) integrants in the human genome are one of the key factors in liver carcinogenesis. Although it is difficult to observe pre/post-HBV infection genomic-level changes in the same clinical sample pairs, they can be observed using artificially infected HBV cell lines such as HepG2.2.15. A detailed HBV integration analysis comparing HepG2.2.15 with HepG2 cells, especially their mitochondrial (mt) DNA, was conducted using next-generation sequencing (NGS)-based integration analysis. Following target DNA enrichment for elements of the HBV genome, NGS was used to identify HBV integration sites in the mtDNA and DNA methylation was analyzed using semi-quantitative pyrosequencing at the boundaries of the integrated region. The results revealed the HBV integration site in the mtDNA of HepG2.215, most notably the insertion of the HBV preCore, X gene fragment in exon 1 of mitochondrially encoded cytochrome C oxidase III (MT-CO3; ChrM 9652), along with a 'CACCA' microhomology sequence. Both boundaries of the integrated region were concordant and highly methylated (HBV side, 92.3%; MT-CO3 side, 95.5%) relative to those observed in nonintegrated HepG2 (4.3%), HepG2.2.15 (3.0%) and PLC/PRF/5 (4.0%) cells. In conclusion, HBV integration sites were successfully identified in the MT-CO3 gene along with a 'CACCA' microhomology sequence using NGS-based analysis and mitochondrial heteroplasmy was identified. The present study also revealed that the HBV/MT-CO3-integrated boundary DNA was hypermethylated at both the HBV and MT-CO3 sides.

Varicella-zoster virus (VZV) can cause visceral disseminated VZV infection in immunocompromised patients. We experienced visceral disseminated VZV infection in an immunocompetent host. A 78-year-old woman visited our hospital complaining of abdominal pain that had persisted for 7 days. On day 3 after admission, a skin rash with blisters appeared mainly on her head and trunk that was diagnosed as generalized zoster via rapid skin VZV diagnostic kit. Esophagogastroduodenoscopy showed gastric erosions, and VZV was detected by real-time polymerase chain reaction testing of the gastric mucosal biopsy specimen. Computed tomography imaging also revealed pancreatitis and colitis, and she was diagnosed as having visceral disseminated VZV infection involving multiple organs. She was treated with acyclovir intravenously, after which her skin rash and abdominal pain disappeared. Because visceral disseminated VZV infection can occur in immunocompetent patients, this disease should be considered in patients with unexplained inflammatory lesions of the gastrointestinal tract or pancreas.

BACKGROUND:Chemotherapies have limited efficacy in pancreatic cancer (PC) and biliary tract cancer (BTC), underscoring the need for new regimens. Recently, tumor-agnostic approaches have been developed for some targeted therapies in advanced solid tumors; however, the frequency of alterations by clinical and genomic background is unclear in PC and BTC. METHODS:To assess the frequencies of druggable gene alterations and investigate new potential therapeutic targetable genomic alterations, advanced PC and BTC patients were tested with comprehensive genomic profiling at Foundation Medicine during the course of clinical care. RESULTS:A total of 16 913 PC patients and 3031 BTC patients were available for analyses, and frequencies of genomic alterations were stratified by age (≥40 years or <40 years), microsatellite instability status, tumor mutational burden status (high ≥10 or low <10 Muts/Mb), and select genomic alterations. Alterations in BRCA2, BRAF, ERBB2, CDK12, PIK3CA, FGFR2, EGFR, and other potential targets were seen across cohorts, with enrichment observed within particular subsets such as in PC patients lacking a KRAS mutation. In BTC patients, the rate of ERBB2 amplification was statistically significantly higher in the tumor mutational burden-high population (23.3% vs 13.7%). Interestingly, CDK12 rearrangement was observed in BTC patients with ERBB2 amplification tumors. In patients younger than 40 years, FGFR2 rearrangement (4%) was observed in PC: GATA6 amplification (11.1%) and rearrangement of BRAF (2.8%)FGFR2 (5.6%) was observed in BTC patients. CONCLUSIONS:We identified an appreciable frequency of immunotherapy biomarkers and targetable gene alterations in both PC and BTC, with notable frequencies in PC samples lacking KRAS mutations and children or adolescent and young adult populations, that should encourage comprehensive genomic profiling testing.

BACKGROUND:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rapidly spreading worldwide, and the resultant disease, coronavirus disease (COVID-19), has become a global pandemic. Although there are multiple methods for detecting SARS-CoV-2, there are some issues with such tests, including long processing time, expense, low sensitivity, complexity, risk of contamination, and user friendly. This study evaluated the reproducibility and usability of a new point-of-care test (POCT) using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) for detecting SARS-CoV-2. METHODS:Samples from 96 patients with suspected SARS-CoV-2 infection were assessed using the real-time qRT-PCR-based POCT and the conventional real-time qRT-PCR method based on the Japanese National Institute of Infectious Diseases guidelines (registration number: jRCT1032200025). RESULTS:The real-time qRT-PCR-based POCT had a positive agreement rate of 90.0% (18/20), a negative agreement rate of 100% (76/76), and a total agreement rate of 97.9% (94/96), and the significantly high score of questionnaire survey (total score p < 0.0001). In the two cases in which real-time qRT-PCR-based POCT results did not match conventional real-time qRT-PCR test results, the SARS-CoV-2 RNA copy numbers were 8.0 copies per test in one case and below the detection limit in the other case when quantified using conventional real-time qRT-PCR. All patients could be triaged within 1 day using the real-time qRT-PCR-based POCT without invalid reports. CONCLUSIONS:The real-time qRT-PCR-based POCT not only had high reproducibility and useability but also allowed rapid patient triage. Therefore, it may be helpful in clinical settings.

4124 Background: Cancers of the pancreas and biliary tract remain one of the unfavorable malignant tumors with few driver genomic alterations. Tumor-agnostic approaches are promising for cancers with poor prognosis, with some potentially actionable alterations, such as BRCA1/2 mutations, ERBB2 amplification, MSI-High, or tumor mutational burden (TMB)-High. However, co-existing alterations, clinical significance of other genomic alterations, or frequency of alterations by clinical and genomic background are unclear. Here we investigated the genomic profile in a large cohort of advanced pancreatobiliary cancers to help refine and discover new targets for improved cancer therapies. Methods: Comprehensive genomic profiling was performed at Foundation Medicine, on patients with RWD tested during the course of routine clinical care. Hybrid capture was carried out on up to 395 cancer-related genes and select introns from up to 31 genes frequently rearranged in cancer. 16,913 pancreatic cancer (PC) patients and 3,031 biliary tract cancer (BTC) patients were available for analyses and were stratified by age (≥40/ < 40), MSI status, TMB status (High ≥10/Low < 10 Muts/Mb), and select gene alterations. Using a chi-square test with Yate’s correction, frequencies of genetic alterations were analyzed according to clinical or genomic background. Results: KRAS (84.8%), TP53 (73.3%), CDKN2A (51.2%), CDKN2B (26.5%), and SMAD4 (23.2%) were frequently altered in PC patients, versus TP53 (60.6%), CDKN2A (33.5%), KRAS (27.1%), CDKN2B (20.6%) and SMAD4 (16.9%) in BTC patients. The frequency of MSI-High and TMB-High in BTC was 1.2% and 5.7%, respectively, while these were lower in PC (0.48% and 2.1%, respectively). In PC patients, the KRAS alteration rate was significantly lower in both MSI-High (57.3%, P< 0.001) and TMB-High populations (51.3%, P< 0.001). In BTC patients, the rate of ERBB2 amplification was 6.4% in TMB-High and 8.6% in TMB-Low population. Interestingly, CDK12 rearrangement was observed in BTC patients with ERBB2 amplified tumors but not in those without ERBB2 amplified tumors. In patients of pediatric/adolescents and young adults ( < 40 years old), the mutation rate of KRAS/ TP53/ CDKN2A/ SMAD4 was lower, and FGFR2 rearrangement (4%) was observed in PC patients; GATA6 amplification (11.1%) and rearrangement of BRAF (2.8%), FGFR2 (5.6%) were observed in BTC patients. Conclusions: A large real-world dataset showed differences in genomic landscape according to clinical or genomic background, and some potential targets for the development of novel drugs in advanced pancreatobiliary cancers. These findings may lead to the improvement of cancer therapies in PC and BTC patients with poor prognosis.

Human papillomavirus (HPV) is a common sexually transmitted infection worldwide, which spreads via contact with infected genital, anal, and oral/pharyngeal areas (oral sex) owing to diverse manners of sexual intercourse. In this study, we devised an oral HPV detection method using mouthwash waste fluids that causes less psychological resistance to visiting the outpatient otolaryngology departments. We successfully detected only the specific unique reverse sequencing probe (using pyro-genotyping) and identified the nine genotypes of HPV targeted for vaccination by pyrosequencing the mouthwash waste fluids of non-head and neck cancer patient volunteers (n = 52). A relatively large number (11/52) of mouthwash waste fluids tested positive for HPV (21.2%; genotype 6, n = 1; 11, n = 1; 16, n = 1; and 18, n = 8). These results surpassed the sensitivity observed testing the same specimens using the conventional method (1/52, 1.9%). Our method (pyro-genotyping) was developed using nine HPV genotypes targeted for vaccination and the results were highly sensitive compared to those of the conventional method. This less expensive, high-throughput, and simple method can be used for detecting oral HPV infection with fewer socio-psychological barriers.

Helicobacter pylori (H. pylori) are a primary factor in the pathogenesis of gastric cancer (GC); GC ranks third among cancer‐related mortality. A clear understanding of the H. pylori genome factors underlying GC is necessary to develop more effective methods to prevent GC. A single‐molecule real‐time DNA sequencing‐based H. pylori genome‐wide association study analysis was performed using the H. pylori genome present in five early‐stage GC (EGC) and five non‐GC clinical DNA samples recovered from gastric washes. A total of 275 genes with 702 nucleotide variants (NVs) were found to be common to three or more patients with EGC but no non‐GC patients (single‐NV: 654/702, 93.2%; multi‐NV: 40/702, 5.7%; deletion: 3/702, 0.4%; insertion: 3/702, 0.7%). Gene ontology analysis of H. pylori revealed that genes involved in the mitochondrial electron transport system, glycolytic processes and the TCA cycle were highly enriched. Cancer‐related NVs were most frequently found in a member of the Helicobacter outer membrane protein family, hopL. In particular, one of the NVs in hopL was a novel six‐nucleotide insertion (1159095̂1159096, TACTTC); this mutant was detected more frequently in a validation set of 50 additional EGC samples (22/50, 44.0%) than in 18 non‐GC samples (3/18, 16.7%, P = .04). These results suggest that the hopL variant is associated with the development of GC and may serve as a genetic biomarker of H. pylori virulence and GC risk. Our assay can serve as a potent tool to expand our understanding of bacteria‐associated tumorigenesis.

polyps.On histopathology fundic gland polyps were most common 141 (38.9 %), followed by hyperplastic 132 (36.4 %) and benign epithelial polyps 61 (16.8%).Other polyps were portal hypertensive polyps 10 (2.7%), Inflammatory polyps 09 (2.4%), Peutz Jegher polyps 04 (1.1%), Neuroendocrine tumor 01 (0.2%) and each case of miscellaneous polyps (leiomyomatous, lipomatous, gastritis cystica profunda and normal gastric mucosa).None of the polyps showed dysplasia, adenoma or malignancy.Conclusion: Prevalence of gastric polyps was 362 (2.8%).Fundic gland polyps were most common, followed by hyperplastic polyps which was likely due to widespread use of proton pump inhibitors.

The eradication of Helicobacter pylori reduces the risk of gastric cancer. A clear understanding of the factors underlying mixed infection with multiple clarithromycin-susceptible and clarithromycin-resistant H. pylori strains is necessary to design more effective therapies against H. pylori . We aimed to assess how the abundance and prevalence of H. pylori strains vary after clarithromycin-based eradication therapy. Using gastric wash samples, which represent the entire stomach, we sequentially analyzed the abundance and prevalence of H. pylori DNA by 23S ribosomal RNA pyrosequencing before and 1, 2, and 3 years after eradication therapy. Low levels of H. pylori DNA were still detectable at the first-year follow-up in all samples with negative post-treatment urea breath test results. The abundance of H. pylori DNA decreased significantly until the 2-year follow-up, but it switched to an increase at the 3-year follow-up. Importantly, the ratio of the prevalence of mutant strains to the prevalence of wild-type strains had already increased at the first-year follow-up and continued to increase, suggesting the selection and growth of clarithromycin-resistant strains during the follow-up periods. Being sensitive and representative, our assay will be useful in effectively addressing gastric cancer development by enhancing the long-term success of intervention strategies and consecutive surveillance for H. pylori eradication.

This case involved an 80-year-old man. Screening with esophagogastroduodenoscopy (EGD) in 2004 revealed Brunner’s gland hyperplasia (BGH), 5 mm in size, in the duodenal bulb. The size of the lesion increased and its shape has changed since then, as detected in subsequent EGDs. The lesion had increased in size to 15 mm with a depression and biopsy specimens revealed an adenocarcinoma. The patient underwent endoscopic mucosal resection. Histopathological assessments indicated an adenocarcinoma arising from gastric foveolar metaplasia (GFM) adjacent to BGH. BGH stained positive for MUC6, and GFM and the adenocarcinoma stained positive for MUC5AC. Mutations of the GNAS gene were not detected in the GFM biopsied in 2007. On the other hand, common GNAS mutations (R201H) were detected in GFM and the adenocarcinoma in the endoscopically resected specimen in 2013. Moreover, mutant allele frequencies were higher in the carcinoma than in GFM. The patient remains disease-free for 4 years after endoscopic treatment. This case report further supports the notion that GFM may be a precursor lesion in the process of GNAS-mutated, gastric-type duodenal carcinogenesis.