Iron deposition in gastric black spots: Clinicopathological insights and NanoSuit-correlative light and electron microscopy analysis.

Objectives: Black spots (BSs) are lentiginous findings observed in the gastric body and fundus during upper gastrointestinal endoscopy and are predominantly seen in patients undergoing Helicobacter pylori eradication treatment. However, the detailed patient background and exact composition are poorly understood. This study aims to clarify the clinicopathological features of BSs, examine patient demographics, and use the NanoSuit-correlative light and electron microscopy (CLEM) method combined with scanning electron microscopy-energy dispersive X-ray spectroscopy for elemental analysis. Methods: Patients who underwent upper gastrointestinal endoscopy between 2017 and 2022 were included. Data on age, medications, blood tests, and H. pylori infection status were retrospectively gathered from medical records. Univariate analysis was conducted to examine BS presence, with results then used in a multivariate model to identify associated risk factors. Additionally, pathological specimens from patients with BSs were analyzed for elemental composition using the NanoSuit-CLEM method combined with scanning electronmicroscopy-energy dispersive X-ray spectroscopy. Results: An analysis of 6778 cases identified risk factors for BSs, including older age and using proton pump inhibitors, statins, corticosteroids, and antithrombotic drugs. Endoscopically, BSs correlated with higher gastric atrophy and lower active H. pylori infection. Iron deposition at BS sites was specifically identified using NanoSuit-CLEM. Conclusions: BSs on gastrointestinal endoscopy may indicate an absence of active H. pylori inflammation. The discovery of iron deposition within BSs using the NanoSuit-CLEM method has offered new insights into the possible causative factors and advances our understanding of the etiology of BSs, bringing us closer to unraveling the underlying mechanisms of their formation.

Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study.

Although immunohistochemistry (IHC) for mismatch repair (MMR) proteins (MMR IHC) is used to identify DNA MMR status, universal screening of all patients with colorectal cancer (CRC) using a combination of both MMR IHC and genetic testing for the BRAFV600E mutation is limited in Japan. This study aimed to better understand the histopathological characteristics of CRCs, which exhibit both deficient mismatch repair (dMMR) and BRAFV600E mutation. MMR IHC of formalin-fixed paraffin-embedded tissues from tumor areas obtained from 651 patients with CRC who underwent surgical resection at Hamamatsu University Hospital (Hamamatsu, Japan) between August 2016 and March 2022 were used to evaluate MMR status, which was determined by staining for the expression of 4 MMR proteins (MLH1, MSH2, PMS2, and MSH6). All dMMR tumors were additionally evaluated for BRAFV600 mutation status via Sanger sequencing. Patient clinical characteristics (age, sex, tumor location, size, and tumor pathology) were then classified using their dMMR and BRAFV600 mutation statuses. Among the 651 patients with CRC, 58 carried tumors with dMMR, of which 52 were deficiency in MLH1 (dMLH1). Interestingly, all 16 medullary carcinomas that were analyzed showed characteristics corresponding to the presence of both dMLH1 and BRAFV600E mutation (P = .01). These results suggest that colorectal medullary carcinomas can be diagnosed based on their unique characteristics of harboring the BRAFV600E mutation and exhibiting dMLH1 expression.

Prostaglandin E-Major Urinary Metabolite Predicts Relapse in Patients With Ulcerative Colitis in Clinical Remission.

INTRODUCTION: Prostaglandin E-major urinary metabolite (PGE-MUM) is a novel biomarker reflecting endoscopic activity in ulcerative colitis (UC). However, there are no studies investigating the efficacy of PGE-MUM as a biomarker for predicting relapse. We investigated whether PGE-MUM can predict clinical relapse of UC. METHODS: The measurement of PGE-MUM and endoscopic evaluation were performed in 70 patients with UC in clinical remission. The optimal cutoff values predicting relapse and relapse-free rate were analyzed. RESULTS: Sixteen patients (22.9%) relapsed during the 12-month follow-up. The median PGE-MUM value of relapsed patients at entry was significantly higher than that of patients in clinical remission (P = 0.008). The cutoff value of PGE-MUM predicting future relapse was 25.2 µg/g Cr by receiver-operating characteristic (ROC) analysis, and the area under the ROC curve was 0.721 (95% confidence interval: 0.556-0.886). The relapse-free rate of patients with PGE-MUM ≥25.2 µg/g Cr was significantly lower than that in patients with PGE-MUM <25.2 µg/g Cr (log-rank test: P < 0.001). The ROC analysis of UC patients with disease duration more than 1-8 years showed that duration of more than 5 years had the largest area under the ROC curve 0.821 (95% confidence interval: 0.583-1.000) and that the optimal cutoff value was 26.3 µg/g Cr. DISCUSSION: PGE-MUM is a reliable biomarker for predicting future relapse, particularly in UC patients with long-disease duration.