Multicenter study of invasive gastric cancer detected after 10 years of Helicobacter pylori eradication in Japan: Clinical, endoscopic, and histopathologic characteristics.

Objectives: Gastric cancer can be diagnosed even in patients long after Helicobacter pylori eradication. Most cases involve intramucosal lesions; however, some are invasive and require surgery. To clarify appropriate long-term surveillance methods, this study compared invasive gastric cancer diagnosed ≥10 and <10 years after eradication. Methods: This retrospective multicenter study included 14 institutions. We included 377 patients with gastric cancer with submucosal or deep invasion after surgical or endoscopic resection. Ordered logistic regression analysis was used to explore the factors contributing to the pathological stage and histological type. Results: Invasive gastric cancer was detected in 84 patients (Group L) and 293 patients (Group S) ≥10 and <10 years after H. pylori eradication, respectively. Endoscopic mucosal atrophy at the time of cancer detection was similar in both groups; 50% of the patients had severe atrophy. Annual endoscopy correlated with early pathological stage (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.14-0.54, p < 0.001). Group L exhibited an independent correlation with the advanced pathological stage (OR 2.27, 95% CI 1.06-4.88, p = 0.035) and the undifferentiated type (OR 2.12, 95% CI 1.16-3.90, p = 0.015). The pure differentiated type and early pathological stage significantly (p = 0.001) correlated with severe mucosal atrophy in Group S but not in Group L. Conclusions: Invasive cancers diagnosed ≥10 years after H. pylori eradication were likely to be more malignant in histological type and pathological stage. Gastric cancer surveillance should continue regardless of endoscopic atrophy, particularly ≥10 years after eradication.

Characterization of residual cancer by comparison of a pair of organoids established from a patient with esophageal squamous cell carcinoma before and after neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) followed by surgery is a standard approach for management of locally advanced esophageal squamous cell carcinoma (ESCC). Patients who do not respond well to NAC have a poor prognosis. Despite extensive research, the mechanisms of chemoresistance in ESCC remain largely unknown. Here, we established paired tumor organoids-designated as PreNAC-O and PostNAC-O-from one ESCC patient before and after NAC, respectively. Although the two organoids did not exhibit significant differences in proliferation, morphology or drug sensitivity in vitro, the tumorigenicity of PostNAC-O in vivo was significantly higher than that of PreNAC-O. Xenografts from PreNAC-O tended to exhibit keratinization, while those from PostNAC-O displayed conspicuous necrotic areas. The tumorigenicity of PostNAC-O xenografts during the chemotherapy was comparable to that of PreNAC-O without treatment. Furthermore, the gene expression profiles of the xenografts suggested that expression of genes involved in the EMT and/or hypoxia response might be related to the tumorigenicity of PostNAC-O. Our data suggested that the tumorigenicity of residual cancer had been enhanced, outweighing the effects of chemotherapy, rather than being attributable to intrinsic chemoresistance. Further studies are required to clarify the extent to which residual cancers share a common mechanism similar to that revealed here.

Usefulness of AI-Equipped Endoscopy for Detecting Colorectal Adenoma during Colonoscopy Screening: Confirm That Colon Neoplasm Finely Can Be Identified by AI without Overlooking Study (Confidential Study).

In the present prospective case series study, we investigated the lesion-detection ability of an AI-equipped colonoscopy as an addition to colonoscopy (CS) screening. Participants were 100 patients aged ≥20 years who had not undergone CS at the study site in the last 3 years and passed the exclusion criteria. CS procedures were conducted using conventional white light imaging and computer-aided detection (CADe). Adenoma detection rate (ADR; number of individuals with at least one adenoma detected) was compared between the conventional group and the CADe group. Of the 170 lesions identified, the ADR of the CADe group was significantly higher than the ADR of the conventional group (69% vs. 61%, p = 0.008). For the expert endoscopists, although ADR did not differ significantly, the mean number of detected adenomas per procedure (MAP) was significantly higher in the CADe group than in the conventional group (1.7 vs. 1.45, p = 0.034). For non-expert endoscopists, ADR and MAP were significantly higher in the CADe group than in the conventional group (ADR 69.5% vs. 56.6%, p = 0.016; MAP 1.66 vs. 1.11, p < 0.001). These results indicate that the CADe function in CS screening has a positive effect on adenoma detection, especially for non-experts.

A case of hepatosplenic cat scratch disease with hemophagocytic lymphohistiocytosis.

Cat scratch disease (CSD) is associated with Bartonella henselae (B. henselae) infection caused by cat scratches or bites. It typically presents with lymphadenitis and fever. However, there are atypical cases such as hepatosplenic CSD, which presents with specific lesions in the liver and spleen. Hemophagocytic lymphohistiocytosis (HLH) is a rare and severe multisystem disorder triggered by infections, cancers, or autoimmune diseases. We experienced a rare case of hepatosplenic CSD with HLH in a non-immunocompromised adult. A 78-year-old woman complained of fever and fatigue. Laboratory tests revealed anemia and liver dysfunction; abdominal contrast-enhanced computed tomography (CT) revealed splenomegaly and nodular hypodense areas in the spleen. In addition, the levels of ferritin and serum soluble IL-2R were markedly elevated, so clinical diagnosis of HLH was made. Positron emission tomography/CT revealed diffuse fluorodeoxyglucose uptake in the liver and spleen suggesting malignant lymphoma, while the pathological findings from liver biopsy suggested infectious diseases. Although she had no cat bites and scratches, she had many cats; therefore, serum B. henselae antibody titers were measured. The B. henselae IgG and IgM titer were 1:128 and 1:20; thus, she was diagnosed with hepatosplenic CSD. Patients with hepatosplenic nodular lesions and contact with cats should be considered for this disease.

Tocilizumab-induced mucosal injury in the terminal ileum mimicking intestinal Behçet's disease: A case report.

RATIONALE: Tocilizumab, a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody, is used for the treatment of adult-onset Still disease (AOSD). Despite its efficacy in many clinical situations, concerns have been raised regarding intestinal mucosal injury in patients receiving tocilizumab. PATIENT CONCERNS: A 64-year-old woman with a history of AOSD was admitted to our hospital with hematochezia. She had AOSD for 15 years and underwent treatment with biweekly tocilizumab 9 months prior to admission. Colonoscopy revealed a large punched-out ulcer in the terminal ileum. On pathological evaluation, nonspecific enteritis with lymphocytes and eosinophils were seen. Based on the location and shape of the lesion, we suspected intestinal Behçet's disease. However, the ulcer reduced in size over time by discontinuation of tocilizumab without additional drug treatment, indicating that it was a drug-induced ulcer. DIAGNOSIS: The patient was diagnosed with tocilizumab-induced small intestinal ulcer. INTERVENTIONS: The patient treated with the discontinuation of tocilizumab. OUTCOMES: The discontinuation of tocilizumab resulted in ulcer scarring. There was no recurrence of hematochezia. LESSONS: Tocilizumab can cause deep ulcerative lesions in the terminal ileum, which may resemble intestinal Behçet's disease. It is important to continuously monitor abdominal symptoms during tocilizumab therapy and aggressively perform colonoscopy when hematochezia or abdominal pain is observed.

A rare presentation of linea alba hernia involving fibrolipoma of the hepatic round ligament: a case report and literature review.

BACKGROUND: Linea alba hernias are relatively rare types of hernias. They manifest as small protrusions situated in the linea alba between the umbilicus and xiphoid cartilage. Usually, hernia contents comprise the pre-peritoneal fat, omentum, and gastrointestinal tract. However, very few cases of linea alba hernias involving the hepatic round ligament have been reported, to date. CASE PRESENTATION: An 80-year-old woman presented with upper abdominal pain and a 1-week history of a mass in the upper midline. Abdominal computed tomography revealed adipose tissue protruding from the abdominal wall contiguous with the hepatic round ligament, suggesting a linea alba hernia. During surgery, the hernial sac content was found to be a mass, which was resected. A linea alba hernia defect measuring 20 mm was repaired using a mesh. Histopathological findings revealed that the mass included mature adipocyte proliferation with broad fibrous septa, which was diagnosed as fibrolipoma of the hepatic round ligament. CONCLUSIONS: We report the first case of a linea alba hernia involving fibrolipoma of the hepatic round ligament worldwide and describe the clinical features, diagnosis, and surgical procedure with a literature review.

The methylation level of a single cancer risk marker gene reflects methylation burden in gastric mucosa.

BACKGROUND: Gastric cancer risk can be accurately predicted by measuring the methylation level of a single marker gene in gastric mucosa. However, the mechanism is still uncertain. We hypothesized that the methylation level measured reflects methylation alterations in the entire genome (methylation burden), induced by Helicobacter pylori (H. pylori) infection, and thus cancer risk. METHODS: Gastric mucosa of 15 healthy volunteers without H. pylori infection (G1), 98 people with atrophic gastritis (G2), and 133 patients with gastric cancer (G3) after H. pylori eradication were collected. Methylation burden of an individual was obtained by microarray analysis as an inverse of the correlation coefficient between the methylation levels of 265,552 genomic regions in the person's gastric mucosa and those in an entirely healthy mucosa. RESULTS: The methylation burden significantly increased in the order of G1 (n = 4), G2 (n = 18), and G3 (n = 19) and was well correlated with the methylation level of a single marker gene (r = 0.91 for miR124a-3). The average methylation levels of nine driver genes tended to increase according to the risk levels (P = 0.08 between G2 vs G3) and was also correlated with the methylation level of a single marker gene (r = 0.94). Analysis of more samples (14 G1, 97 G2, and 131 G3 samples) yielded significant increases of the average methylation levels between risk groups. CONCLUSIONS: The methylation level of a single marker gene reflects the methylation burden, which includes driver gene methylation, and thus accurately predicts cancer risk.

Differences in clinical features and morphology between differentiated and undifferentiated gastric cancer after Helicobacter pylori eradication.

BACKGROUND/AIMS: Although undifferentiated gastric cancer (UGC) diagnosed after Helicobacter pylori eradication (HPE) carries a poor prognosis, characteristics of post-HPE UGC have not been evaluated in detail because of its low incidence. Therefore, we compared the clinicopathologic characteristics of UGC and differentiated gastric cancers (DGC) diagnosed after successful HPE. METHODS: GC lesions from patients who had successfully completed HPE and who had undergone upper gastrointestinal endoscopy between January 2004 and March 2016 were analyzed. Tumors were divided into DGC and UGC groups. Clinicopathologic factors of background and tumor characteristics were compared using univariate and multiple logistic analyses. RESULTS: A total of 129 tumors from 115 patients were evaluated; 113 tumors were in the DGC group and 16 in the UGC group. Depressed-type tumors (P = 0.024) and sub-submucosal invasion (P<0.001) were significantly higher in the UGC group. The UGC group had larger tumor diameters (25.9±7.3 mm) than the DGC group (13.2±10.2 mm) (P<0.001). Multivariate analysis showed that female sex (odds ratio [OR] 3.24, 95%CI:1.02-10.37; P = 0.047) and absent follow-up (OR 4.99, 95%CI:1.60-15.57; P = 0.006) were significant independent risk factors for UGC. The DGC group showed a gradually decreasing temporal trend by trend test (P = 0.015), while the UGC group showed a relatively constant incidence over time, although the number of cases was small. CONCLUSION: UGC was diagnosed even after long time spans following HPE, although the number of cases was small. Female sex, and especially absent follow-up, were risks for post-HPE UGC, suggesting that diligent long-term follow-up after HPE is essential.

Efficient Establishment of Bile-Derived Organoids From Biliary Cancer Patients.

Patient-derived tumor organoids have considerable potential as an in vitro diagnostic tool for drug susceptibility testing. In the present study, we investigated whether bile collected for diagnostic purposes could be a potential source for the establishment of biliary cancer organoids. Among 68 cases of biliary cancer, we successfully generated 60 bile-derived organoids (BDOs) from individual patients. Consistent with previous reports that described biliary cancer organoids from surgical tissues, the BDOs showed diverse morphologies such as simple cysts, multiloculated cysts, thick capsulated cysts, and solid masses. They also harbored mutations in KRAS and TP53 at frequencies of 15% and 55%, respectively. To enrich the cancer organoids by removing contaminated noncancerous components of BDOs, we attempted to verify the effectiveness of 3 different procedures, including repeat passage, xenografting, and selection with an MDM2 inhibitor for TP53 mutation-harboring BDOs. By monitoring the sequence and expression of mutated TP53, we found that all these procedures successfully enriched the cancer organoids. Our data suggest that BDOs can be established with minimal invasiveness from almost all patients with biliary cancers, including inoperable cases. Thus, despite some limitations with respect to the characterization of BDOs and methods for the enrichment of cancer cell-derived organoids, our data suggest that BDOs could have potential applications in personalized medicine.

Comparison of the improvement in gastric mucosal tissue after Helicobacter pylori eradication between young and elderly people.

BACKGROUND AND STUDY AIMS: Helicobacter pylori (H. pylori) infection has been clearly shown to be a cause of gastric cancer, and the incidence of gastric cancer has been shown to decrease with eradication. However, few reports have described the utility of eradication therapy in elderly people. Thus, an investigation focusing on how much actual histological improvement is obtained with eradication therapy in elderly people was conducted. PATIENTS AND METHODS: This was a retrospective study conducted using medical information of patients diagnosed with H. pylori-associated gastritis and who underwent eradication therapy. The histological improvement was assessed based on changes in the atrophy and intestinal metaplasia scores of the Updated Sydney system from before to after eradication. We investigated the rates of histological improvement in atrophy and intestinal metaplasia one year after and long term more than five years after H. pylori eradication in an elderly group and a younger group. RESULTS: This study included 221 patients (elderly group 123, younger group 98). In histological atrophy, higher rates of improvement were seen in the corpus than in the antrum, and the rates of cure in the antrum were lower in elderly group than in younger group (p = 0.0282). With regard to intestinal metaplasia, the rates of improvement in the antrum were lower in elderly group than in younger. In long term observation, although the rates of cure in the antrum were lower in elderly, improvements were seen in atrophy scores in most of the patients and intestinal metaplasia scores in about half of patients. CONCLUSION: Though there is more obvious improvement in the gastric mucosa when H. pylori eradication therapy is performed at a young age, some mucosal improvement can be expected in about half of patients after eradication, even in elderly people.

Pancreatic cancer with pseudoaneurysm after duckbill-shaped anti-reflux metal stent placement: A case report.

A 74-year-old man was diagnosed with unresectable pancreatic cancer with obstructive jaundice. Chemotherapy with gemcitabine and nab-paclitaxel was initiated after placement of a duckbill-shaped anti-reflux metal stent (D-ARMS). A period of 1 month after D-ARMS placement, the patient developed hematemesis and entered severe shock following emergency admission for further evaluation. Contrast-enhanced computed tomography revealed a pseudoaneurysm in the gastroduodenal artery, coincident with the site of D-ARMS placement, and bleeding from the same site was diagnosed. Angiography was performed, and the pseudoaneurysm was successfully treated by transcatheter arterial embolization using coils. The patient was subsequently discharged from hospital and experienced no further bleeding until his death due to an aggravation of the pancreatic cancer after 2 months. We report a case of pancreatic cancer with pseudoaneurysm after D-ARMS placement.

Acute Cholecystitis Associated with Eosinophilic Granulomatosis with Polyangiitis That Responded to Glucocorticoid Therapy.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic disorder characterized by tissue eosinophilic infiltration and vasculitis. Although EGPA causes multiple organ damage, it causes cholecystitis less frequently. We herein report a case of acute cholecystitis associated with EGPA in which successful treatment with glucocorticoid therapy allowed surgery to be avoided. EGPA can present as acute cholecystitis. It is important not to overlook acute cholecystitis associated with EGPA in patients with abdominal pain with peripheral eosinophilia. Furthermore, in cases of mild cholecystitis associated with EGPA that are diagnosed preoperatively, cholecystectomy might be avoided with conservative glucocorticoid treatment.

Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study.

BACKGROUND: Although eradication therapy for chronic Helicobacter pylori (H. pylori) reduces the risk of gastric cancer (GC), its effectiveness is not complete. Therefore, it is also critically important to identifying those patients who remain at high risk after H. pylori eradication therapy. Accumulation of protein methylation is strongly implicated in cancer, and recent study showed that dimethylation of eEF1A lysine 55 (eEF1AK55me2) promotes carcinogenesis in vivo. We aimed to investigate the relationship between eEF1A dimethylation and H. pylori status, efficacy of eradication therapy, and GC risk in H. pylori-eradicated mucosa, and to reveal the potential downstream molecules of eEF1A dimethylation. METHODS: Records of 115 patients (11 H. pylori-negative, 29 H. pylori-positive, 75 post-eradication patients) who underwent upper gastrointestinal endoscopy were retrospectively reviewed. The eEF1A dimethyl level was evaluated in each functional cell type of gastric mucosa by immunofluorescent staining. We also investigated the relationship between eEF1AK55me2 downregulation by CRISPR/Cas9 mediated deletion of Mettl13, which is known as a dimethyltransferase of eEF1AK55me2. RESULTS: The level of eEF1A dimethylation significantly increased in the surface and basal areas of H. pylori-positive mucosa compared with the negative mucosa (surface, p = 0.0031; basal, p = 0.0036, respectively). The eEF1A dimethyl-levels in the surface area were significantly reduced by eradication therapy (p = 0.005), but those in the basal area were maintained even after eradication therapy. Multivariate analysis revealed that high dimethylation of eEF1A in the basal area of the mucosa was the independent factor related to GC incidence (odds ratio = 3.6611, 95% confidence interval = 1.0350-12.949, p = 0.0441). We also showed the relationship between eEF1A dimethylation and expressions of reprogramming factors, Oct4 and Nanog, by immunohistochemistry and in vitro genome editing experiments. CONCLUSIONS: The results indicated that H. pylori infection induced eEF1A dimethylation in gastric mucosa. The accumulation of dimethyl-eEF1A in the basal area of the mucosa might contribute to GC risk via regulation of reprograming factors in H. pylori eradicated-gastric mucosa.

Analysis of long-term serological and histological changes after eradication of Helicobacter pylori.

Stratification of gastric cancer risk by measuring serological biomarkers is useful for screening of gastric cancer. However, this method has problem such as overlooking past infected patients. We aimed to evaluate the association between Helicobacter pylori infection status and serological biomarkers. We divided 5,268 patients according to Helicobacter pylori infection status and past infected patients were divided into 12 groups according to time elapsed since eradication. We analyzed mean serum H. pylori immunoglobulin G antibody, pepsinogen titers, histological and endoscopic atrophy score of each group. Mean H. pylori immunoglobulin G antibody showed a decreasing tendency, there was no significant difference from the uninfected group at 11 years after eradication (p = 0.19). PGI, PGII decreased in short term after eradication. However, both PGI and PGII gradually increased as long-term changes after eradication, became comparable to those in the uninfected group (p = 0.41, p = 0.37, respectively). Histological atrophy improved gradually, became equivalent to uninfected group. Endoscopic atrophy score did not improve for long term after eradication. In conclusion, patients with long term after eradication reach the uninfected condition serologically, histologically. Endoscopic assessment of gastric mucosal atrophy may be useful for accurate assessment of gastric cancer risk.

Clinicopathological characteristics of pancreatic acinar cell metaplasia associated with Helicobacter pylori infection.

BACKGROUND: Pancreatic acinar cell metaplasia (PACM) has been rarely reported in the gastric mucosa. In the present study, we aimed to elucidate the clinical and pathological characteristics of PACM associated with Helicobacter pylori (H. pylori). METHOD: 5930 patients who underwent five- or two-point gastric biopsy according to the updated Sydney system (USS) by upper gastrointestinal endoscopy were enrolled. The patients were categorized into current H. pylori infection (CHI), post-H. pylori eradication (PHE), and non-H. pylori infection (NHI) groups according to the H. pylori infection status, and the frequency and location of PACM were compared. Additionally, a case-control study was performed to compare the USS scores between patients with CHI and PACM and those with CHI but not PACM. RESULT: The frequencies of PACM were 0.49% (10/2039), 0.75% (25/3332), and 0% (0/559) in the CHI, PHE, and NHI groups, respectively. PACM was found in the greater curvature of the antrum in 33 of the 35 patients with PACM. Among the patients with CHI, the inflammation scores in the greater curvature of the antrum and the greater curvature of the corpus were lower in patients with PACM than in those without PACM. CONCLUSION: Although rarely reported in the gastric mucosa, PACM was closely related to H. pylori infection, especially in the antrum, and was associated with relatively mild inflammation.

Changes in Gastric Mucosal Glycosylation Before and After Helicobacter pylori Eradication Using Lectin Microarray Analysis.

BACKGROUND: Glycosylation is a common post-translational modification, and it has been reported that alterations in the glycosylation patterns on cells are related to cell proliferation, differentiation, tissue adhesion, and carcinogenesis. This study aimed to investigate the relationship between Helicobacter pylori infection and gastric mucosal glycosylation using a lectin microarray system. METHODS: Gastric mucosal samples were obtained from 10 Helicobacter pylori-non-infected patients, 10 H. pylori-infected patients, and 10 after H. pylori-eradicated patients who underwent gastric mucosal biopsy by endoscopy in our institute. The gastric gland cells which were isolated from formalin-fixed, paraffin-embedded gastric mucosal biopsy samples using laser capture microdissection were used for lectin microarray to obtain lectin-glycan interaction values. RESULTS: Comparison of the lectin-glycan interaction values before and after eradication in the same patients showed significant increases for Ricinus communis agglutinin 120, Trichosanthes japonica agglutinin II, Euonymus europaeus lectin, jacalin, Amaranthus caudatus agglutinin, and Maclura pomifera agglutinin and significant decreases for Urtica dioica agglutinin, Lycopersicon esculentum lectin, Ulex europaeus agglutinin, Sambucus nigra agglutinin, Sambucus sieboldiana agglutinin, and Trichosanthes japonica agglutinin I. Furthermore, jacalin and MPA in the gastric antrum were significantly decreased with H. pylori infection compared with the without infection group and improved to the levels seen without infection as a result of eradication. Lycopersicon esculentum lectin, Sambucus nigra agglutinin, Sambucus sieboldiana agglutinin, and Trichosanthes japonica agglutinin I in the gastric body were significantly increased with H. pylori infection and improved to the level seen without infection as a result of eradication. CONCLUSION: H. pylori infection changes the lectin binding state which is related to various cancers on the gastric mucosal cell. Furthermore, those changes are reversible by H. pylori eradication.

Genome-wide association study of gastric cancer- and duodenal ulcer-derived Helicobacter pylori strains reveals discriminatory genetic variations and novel oncoprotein candidates.

Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori, which causes gastric cancer. We conducted a small-sample GWAS (125 gastric cancer cases and 115 controls) followed by prediction of gastric cancer and control (duodenal ulcer) H. pylori strains. We identified 11 single nucleotide polymorphisms (eight amino acid changes) and three DNA motifs that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into gastric cancer pathogenesis and a basis for identifying a set of biomarkers for distinguishing these H. pylori-related diseases.

Immunohistochemical differences in gastric mucosal damage between nodular and non-nodular gastritis caused by Helicobacter pylori infection.

In this study, the level of cell damage were analyzed immuno-histochemically to clarify the association between nodular gastritis and undifferentiated gastric cancer. Thirty patients of nodular gastritis were enrolled as the nodular gastritis group. Thirty patients of non-nodular gastritis were enrolled as the control group. They were evaluated according to the updated Sydney system and used for immunohistochemical staining (p53, Ki-67, E-cadherin, and 8-OHdG). The scores based on the updated Sydney system were significantly higher in the nodular group than in the non-nodular group for histologically assessed inflammation and activity in the gastric corpus (1.91 ±â€„0.77 vs 1.58 ±â€„0.60, p = 0.049, 0.83 ±â€„0.81 vs 0.44 ±â€„0.64, p = 0.032). On immunostaining, the detection of E-cadherin was lower in the nodular group for both the antrum (1.0 ±â€„0.62 vs 1.47 ±â€„0.85, p = 0.047) and the corpus (1.16 ±â€„0.81 vs 1.48 ±â€„0.71, p = 0.043) and the p53 labeling index of the gastric corpus was higher in the nodular group than in the non-nodular group (3.06 ±â€„1.94 vs 2.03 ±â€„1.99, p = 0.015). Nodular gastritis showed significant severe inflammation and immunohistochemical cell damage compared with non-nodular gastritis. These findings may play an important role in the oncogenesis of undifferentiated gastric cancer in nodular gastritis.

Early response in phosphorylation of ribosomal protein S6 is associated with sensitivity to trametinib in colorectal cancer cells.

Mutations in RAS or BRAF are associated with poor prognosis and resistance to epidermal growth factor receptor (EGFR)-targeted therapy in colorectal cancer (CRC). Despite their common ability to activate downstream genes such as MEK and ERK, the therapeutic benefit of MEK inhibitors for patients with RAS/BRAF mutant CRC is limited, highlighting the need for biomarkers to predict the efficacy of MEK inhibition. Previously, we reported that a change in phosphorylation of ribosomal protein S6 (pS6) after MEK inhibition was significantly associated with sensitivity to MEK inhibition in gastric cancer cells. Here, we investigated the value of the response in pS6 for predicting the efficacy of trametinib, a MEK inhibitor, in patients with RAS/BRAF mutant CRC using patient-derived CRC organoids. We found that a subset of CRC cell lines and organoids were sensitive to trametinib. The change in phosphorylated ERK, a downstream molecule of the RAS/RAF/MEK pathway, was not significantly associated with trametinib sensitivity. On the other hand, only those with sensitivity showed a reduction of pS6 levels in response to trametinib. The change in pS6 after trametinib treatment was detectable by Western blotting, immunohistochemistry or immunocytochemistry. We also demonstrated an impact of MEK inhibition on pS6 in vivo using a xenograft model. Our data suggest that, in combination with patient-derived organoids, immunostaining-based detection of pS6 could be useful for prediction of trametinib sensitivity.