Injury to the Muscle Layer and Risk of Non-cardiac Chest Pain after Endoscopic Submucosal Dissection for Esophageal Cancer.

BACKGROUND AND AIMS: Non-cardiac chest pain (NCCP) is a frequent complication of endoscopic submucosal dissection (ESD) for early-stage esophageal cancer. However, little is known about relationships between ESD findings and NCCP. This study aims to evaluate the risk factors for NCCP, including ESD findings related to injury to the muscle layer. METHODS: We enrolled a total of 296 lesions from 270 patients with esophageal squamous cell carcinoma (ESCC), who underwent ESD in our center. The grade of injury to the muscle layer caused by ESD was categorized as follows: grade 0: no exposure of muscularis propria; grade 1: muscularis propria exposure and/or whitish color change by the electrocoagulation; grade 2: torn muscularis propria with whitish color change by the electrocoagulation; and grade 3, esophageal perforation. The risk factors for NCCP, including ESD findings, were analyzed by univariate and multivariate analyses. RESULTS: NCCP occurred in 89 patients (33.0%) after esophageal ESD. Multivariate analysis demonstrated that younger age [odds ratio (OR) 0.95, 95% confidence interval (95%CI) 0.92-0.98, p=0.003), postoperative fever (>= 38°C) (OR=25.9, 95%CI: 2.89-232.10, p=0.004), ESD findings (grade 1: OR=3.99, 95%CI: 1.63-9.75, p=0.003 and grade 2: OR=3.18, 95%CI: 1.54-6.57, p=0.002) were independently associated with the incidence of post ESD NCCP. CONCLUSIONS: ESD findings relate to slight Injury to the muscle layer, such as muscularis propria exposure and whitish color change by the electrocoagulation were identified as risk factor for post ESD NCCP. We should therefore perform esophageal ESD carefully to avoid injuring the muscle layers.

Microarchitectures of Barrett's esophagus associated with DNA methylation status.

Aim: DNA methylation is involved in esophageal adenocarcinoma (EAC) and Barrett's esophagus (BE). Microarchitectures of on-neoplastic BE associated with DNA methylation status were examined using magnifying narrow-band imaging (NBI) endoscopy. Patients and methods: Using biopsies from non-neoplastic BE without cancer (n = 66; N group), with EAC (n = 27; ADJ group) and EAC tissue (n = 22; T group), methylation of N33, DPYS, SLC16A12, miR124a3 and miR34bc genes were quantified. Magnifying NBI features of non-neoplastic BE were classified according to their morphologies. Results: The ADJ and T groups presented higher DNA methylation compared with the N group. Magnifying NBI endoscopic features of non-neoplastic BE also correlated with DNA methylation as an independent factor. Conclusion: Microarchitectures of BE visualized by magnifying NBI endoscopy correlated with DNA methylation.

Combined serum albumin, fecal immunochemical test, and leucine-rich alpha-2 glycoprotein levels for predicting prognosis in remitting patients with ulcerative colitis.

This study investigated the usefulness of serum leucine-rich alpha-2 glycoprotein (LRG) and fecal immunochemical tests (FIT) for predicting relapse in patients with ulcerative colitis (UC). Data of 194 patients tested for LRG between January 2020 and June 2022 were retrospectively collected and clinical characteristics were recorded. LRG was strongly correlated with CRP levels and it had a moderately negative correlation with albumin levels, whereas FIT was not significantly correlated with either CRP or albumin levels. Furthermore, the median serum albumin and FIT were significantly different between patients with or without clinical relapse; while the LRG level was not associated with clinical relapse. Although LRG is not an independent factor for predicting clinical relapse, the cumulative remission rate was significantly higher in patients with higher albumin than in those with lower albumin. Furthermore, the combination of FIT and albumin was useful for predicting for relapse, patients with higher FIT and lower albumin tended to have higher relapse rates than those with both lower FIT and albumin and those with lower FIT and higher albumin. Our study indicated that serum albumin level is useful for predicting relapse, even in remitting outpatients. Although LRG is not an independent factor for predicting clinical relapse, it is useful for identifying patients that are likely to relapse when combined serum albumin or FIT results.

Intravenous injection of tumor extracellular vesicles suppresses tumor growth by reducing the regulatory T cell phenotype.

BACKGROUND: Colorectal cancer is a disease of unmet medical need. Although extracellular vesicles (EVs) have been implicated in anti-tumor responses, discrepancies were observed among studies. We analyzed the role of tumor-derived EVs (TEVs) in tumor progression in vivo by focusing on regulatory T (Treg) cells, which play essential roles in tumor development and progression. METHODS: A mouse model of colorectal cancer lung metastasis was generated using BALB/c mice by tail vein injection of the BALB/c colon adenocarcinoma cell line Colon-26. TEVs derived from Colon-26 and BALB/c lung squamous cell carcinoma ASB-XIV were retrieved from the culture media supernatants. A TEV equivalent to 10 µg protein was injected every other day for 2 weeks. RESULTS: Histology and immunohistochemistry studies revealed that lung tumors reduced in the Colon-26-EV group when compared to the phosphate-buffered saline (PBS) group. The population of CD4 + FoxP3 + cells in the lung was upregulated in the PBS group mice when compared to the healthy mice (P < 0.001), but was significantly downregulated in the Colon-26-EV group mice when compared to the PBS group mice (P < 0.01). Programmed cell death protein 1, glucocorticoid-induced TNFR-related protein, and CD69 expression in lung Treg cells were markedly upregulated in the PBS group when compared to the healthy mice, but downregulated in the Colon-26-EV group when compared to the PBS group. The changes in expression were dose-dependent for Colon-26-EVs. ASB-EVs also led to significantly downregulated Treg cell expression, although non-cancer line 3T3-derived EVs did not. CONCLUSION: Our study suggests that TEVs possess components for tumor suppression.

Usefulness of texture and color enhancement imaging (TXI) in early gastric cancer found after Helicobacter pylori eradication.

Early-stage gastric cancer (EGC) found after Helicobacter pylori (Hp) eradication is often difficult to diagnose using conventional white light (WL) endoscopy. We aimed to evaluate whether Texture and Color Enhancement Imaging (TXI), a new image-enhanced endoscopy enhances the EGC lesions after Hp eradication. We also compared diagnostic accuracy and lesion detection time between WL and TXI in trainee endoscopists. 58 EGC lesions after successful Hp eradication were enrolled. Using endoscopic images in WLI, TXI mode 1 (TXI1), and TXI mode 2 (TXI2), visibility of EGC was assessed by six expert endoscopists using a subjective score. Mean color differences (ΔE) of four matched adjacent and intra-tumoral points were examined. Using randomly allocated images, diagnostic accuracy and lesion detection time were evaluated in three trainee endoscopists. Visibility score was unchanged (Score 0) in 20.7% (12/58) and 45.6% (26/57), slightly improved (Score 1) in 60.3% (35/58) and 52.6% (30/57), obviously improved (Score 2) in 45.6% (26/58) and 1.8% (1/57), in TXI1 and TXI2 compared to WL, respectively. Mean ΔE ± SEM in TXI1 (22.90 ± 0.96), and TXI2 (15.32 ± 0.71) were higher than that in WL (1.88 ± 0.26, both P < 0.0001). TXI1 presented higher diagnostic accuracy compared to WL, in two of three trainees (94.8% vs. 74.1%, 100% vs. 89.7%, P = 0.003; < 0.005, respectively). Lesion detection time was shorter in TXI1 in two of three trainees (P = 0.006, 0.004, respectively) compared to WL. TXI improves visibility of EGC after Hp eradication that may contribute to correct diagnosis.

Large Metastatic Cardiac Tumor from Ascending Colon Cancer with Autopsy.

A metastatic cardiac tumor from colon cancer is an exceedingly rare clinical feature associated with a poor prognosis without therapeutic intervention; however, such cases may be frequently encountered in clinical practice, especially among the elderly. We report a case of synchronous double cancer of the prostate and ascending colon with metastases to multiple organs, including a large cardiac tumor. A 71-year-old Japanese man had prostate cancer with neck and para-aortic metastasis. He visited our hospital with complaints of fatigue and a positive fecal occult blood test result. Colonoscopy findings revealed the presence of a tumor in the ascending colon, and contrast-enhanced CT revealed a tumor in the heart, which was possibly due to metastasis from the ascending colon. The patient received palliative care and declined anticancer treatment. He died due to respiratory failure 3 months after the first diagnosis but did not show critical arrhythmia until death. Autopsy revealed the presence of a large mass in the right ventricle with tumor embolism of the right coronary artery. The cardiac mass was pathologically consistent with metastasis from the colon. In case of colorectal cancer with cardiac metastasis involving poor prognosis or performance status, best supportive care without any therapeutic intervention could be the optimal treatment for the quality of the remaining time.

Extracellular vesicles microRNA analysis in type 1 autoimmune pancreatitis: Increased expression of microRNA-21.

BACKGROUND: The molecular basis of type 1 autoimmune pancreatitis (AIP) remains unclear. Recent attention on the role of extracellular vesicles microRNA (EV miRNA) in immune homeostasis has prompted us to perform an extensive miRNA screening of serum-derived EV in AIP. METHODS: EV miRNA expression was analyzed using microarrays in AIP, chronic pancreatitis (CP), and healthy adult (HC) samples (n = 10 from each group). Differences in signals, > 3 or <1/3 times, represented significant differences in expression. Another cohort of AIP (n = 14), CP (n = 10), and HC (n = 10) samples of EV miRNA was analyzed using reverse-transcription polymerase chain reaction (RT-PCR). miRNA expression in pancreatic tissues was evaluated using in situ hybridization (ISH) in three additional subjects from each group. RESULTS: Signals of eight miRNAs (miR-659-3p, -27a-3p, -99a-5p, -21-5p, -205-5p, -100-5p, -29c-3p, and -125b-1-3p) were significantly higher, while those of two miRNAs (miR-4252 and -5004-5p) were significantly lower in AIP than in HC. EV miR-21-5p was significantly up-regulated in AIP than in HC (P = 0.035) and CP (P = 0.048). The number of miR-21-5p positive inflammatory cells was significantly elevated in AIP than in CP (P = 0.014). CONCLUSIONS: Circulating EVs exhibited altered miRNA expression patterns with elevated miR-21-5p in AIP when compared with those in HC and CP. miR-21-5p was highly expressed in pancreatic inflammatory cells in AIP. Our data suggests that miR-21-5p may be involved in the regulation of effector pathways in the pathophysiology of AIP, thus differentiating AIP from CP.

Diffuse Pancreatic Cancer Mimicking Autoimmune Pancreatitis.

The characteristic finding of sausage-shaped pancreas or capsule-like rim facilitates the diagnosis of autoimmune pancreatitis. We herein report a case of a 67-year-old man showing a sausage-shaped, enlarged pancreas with a capsule-like rim on computed tomography. Furthermore, endoscopic retrograde cholangiopancreatography demonstrated diffuse narrowing of the main pancreatic duct, in addition to stenosis of the lower bile duct. Finally, we were able to diagnose pancreatic cancer in this patient by an endoscopic ultrasound-guided fine-needle aspiration biopsy following peroral cholangioscopy and bile cytology. This report emphasizes the significance of pathological confirmation before starting treatment, even in cases with diffuse pancreatic enlargement.