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.

Effect of disease duration on fecal biomarkers in ulcerative colitis: a prospective cohort study.

BACKGROUND: Biomarkers such as fecal calprotectin (FC) and fecal immunochemical occult blood tests (FIT) for ulcerative colitis (UC) are used in clinical practice. In this study, the effect of UC disease duration on FC was investigated and compared to that on FIT. METHODS: One hundred twenty-eight colonoscopic examinations and two fecal biomarkers measurements were performed. The cases of UC were divided into short- and long-term disease-duration groups or categorized into three groups with disease durations of 0-5, 6-13, and 14-38 years. We analyzed correlations between biomarker levels and endoscopic scores, including the Mayo endoscopic subscore (MES), ulcerative colitis endoscopic index of severity, and the sum of MES. RESULTS: In the analysis of short- and long-term disease durations, the three endoscopic scores and biomarker levels showed significant correlations in both long-term and short-term groups. Most of the correlation coefficients for the individual long-term group were lower than the corresponding values for all cases, while most of the correlation coefficients for the individual short-term groups were higher than the corresponding values for all cases. In the three-group analysis (disease durations of 0-5, 6-13, and 14-38 years), the two biomarkers and three endoscopic scores showed significant correlations, and most of the correlation coefficients between biomarkers and endoscopic scores tended to be lower in the long-term follow-up group. In the receiver operating characteristic analysis for predicting mucosal healing in the three groups, the area under the curve for FC and FIT concentrations in the 0-5 year disease-duration group showed particularly higher values than those for the other two groups. CONCLUSIONS: Similar to FIT, FC is affected by the duration of UC, indicating that FC may be a highly useful biomarker, especially in short-term disease.

DNA mismatch repair is not disrupted in stage 0 colorectal cancer resected using endoscopic submucosal dissection.

The frequency of deficient mismatch repair (dMMR) or microsatellite instability-high colorectal cancer (CRC) is estimated to be ~15% of all patients with CRC; however, the patients reported are limited to surgical cases, and the frequency of patients exhibiting stage 0 disease is not considered, despite the currently increasing use of endoscopic techniques to cure a number of these patients. In the present study, the DNA MMR status for stage 0 patients with CRC treated using endoscopic submucosal dissection or endoscopic mucosal resection was analyzed via immunohistochemical staining of four types of proteins, namely MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6 and PMS1 homolog 2 MMR system component, in adenocarcinoma specimens. Notably, none of the endoscopically resected specimens exhibited dMMR among the 41 patients diagnosed with stage 0 CRC. Since tumors harboring dMMR progress more rapidly than tumors with chromosomal instability, the present results highlight the importance of tumor resection during very early phases that exist before the promoter region of MLH1 becomes hypermethylated, resulting in a loss of DNA MMR function.

Photodynamic Therapy Using Talaporfin Sodium for Local Failure after Chemoradiotherapy or Radiotherapy for Esophageal Cancer: A Single Center Experience.

A phase II study of second-generation photodynamic therapy (PDT) using talaporfin sodium has shown excellent treatment results for esophageal cancer with local failure after chemoradiotherapy (CRT) or radiotherapy (RT). However, only a few studies have reported this therapy in clinical practice. This study aimed to confirm the efficacy and safety of salvage PDT using talaporfin sodium for esophageal cancer in various clinical situations. Twelve patients with esophageal cancer with local failure after definitive CRT or RT who underwent PDT using talaporfin sodium were enrolled from April 2016 to January 2020. Overall, 10 patients (83.3%) achieved a local complete response. No skin phototoxicity was observed, but esophageal stricture occurred in five patients (41.7%). Esophageal stricture was improved with endoscopic balloon dilation in all patients, and subsequent analysis found no significant factors causing esophageal stricture after PDT. Two patients with synchronous tumors were successfully rescued by combination therapy with endoscopic submucosal dissection. Two patients with carcinoma in situ of larger than 1/2 circumference were rescued by repeated PDT. The 2-year overall survival was 80.0% (95% confidence interval 0.409-0.946). PDT using talaporfin sodium was an effective and safe salvage treatment for esophageal cancer with local failure after CRT or RT in various clinical situations.

[Schistosomiasis japonica in a patient who emigrated from China: a case report].

A 37-year-old woman exhibited abnormal liver enzyme levels without any symptoms at a medical check-up. She was born and raised in Hubei, China, and had immigrated to Japan in her mid-thirties. Ultrasonography revealed an enlarged caudate lobe of the liver and a wide moniliform portal vein, whereas computed tomography revealed lined calcification on the surface of the liver and on the collateral vein of the portal vein. Although imaging studies provided no critical findings, the crucial information that led to diagnosis was gained through the interview with the patient. Schistosomiasis japonica was known to be prevalent in her hometown, and she reported that her father's past infection was due to Schistosoma japonicum. Serological analysis demonstrated high levels of anti-S. japonicum antibodies, which were reduced using praziquantel administration.

Acid suppressive therapy improved symptoms due to circumferential cervical inlet patch with proton pumps (H+/K+-ATPase).

Cervical inlet patch (CIP), also referred to as esophageal heterotopic gastric mucosa, is regarded as the residue of columnar epithelium of the embryonic esophagus. Narrow band imaging increases the detection rate of CIP. Herein, we present a 55-year-old man with symptomatic circumferential inlet patch. He exhibited globus and dysphagia, and esophagogastroduodenoscopy found cir-cumferential CIP, where im-munohistochemistry revealed the existence of pro-ton pumps (H+, K+-ATPase). His throat symptoms were relieved by acid suppressive therapy with pump inhibitors. This case indicated that CIP should be considered as a differential diagnosis for the cause of globus symptoms in rare cases.