Early detection of pancreatic cancer by comprehensive serum miRNA sequencing with automated machine learning.

BACKGROUND: Pancreatic cancer is often diagnosed at advanced stages, and early-stage diagnosis of pancreatic cancer is difficult because of nonspecific symptoms and lack of available biomarkers. METHODS: We performed comprehensive serum miRNA sequencing of 212 pancreatic cancer patient samples from 14 hospitals and 213 non-cancerous healthy control samples. We randomly classified the pancreatic cancer and control samples into two cohorts: a training cohort (N = 185) and a validation cohort (N = 240). We created ensemble models that combined automated machine learning with 100 highly expressed miRNAs and their combination with CA19-9 and validated the performance of the models in the independent validation cohort. RESULTS: The diagnostic model with the combination of the 100 highly expressed miRNAs and CA19-9 could discriminate pancreatic cancer from non-cancer healthy control with high accuracy (area under the curve (AUC), 0.99; sensitivity, 90%; specificity, 98%). We validated high diagnostic accuracy in an independent asymptomatic early-stage (stage 0-I) pancreatic cancer cohort (AUC:0.97; sensitivity, 67%; specificity, 98%). CONCLUSIONS: We demonstrate that the 100 highly expressed miRNAs and their combination with CA19-9 could be biomarkers for the specific and early detection of pancreatic cancer.

Anti-integrin αvß6 autoantibodies are a potential biomarker for ulcerative colitis-like immune checkpoint inhibitor-induced colitis.

BACKGROUND: No specific biomarker for immune checkpoint inhibitor (ICI)-induced colitis has been established. Previously, we identified anti-integrin αvß6 autoantibodies in >90% of patients with ulcerative colitis (UC). Given that a subset of ICI-induced colitis is similar to UC, we aimed to clarify the relationship between such autoantibodies and ICI-induced colitis. METHODS: Serum anti-integrin αvß6 autoantibody levels were compared between 26 patients with ICI-induced colitis and 157 controls. Endoscopic images of ICI-induced colitis were centrally reviewed. Characteristics of anti-integrin αvß6 autoantibodies in the ICI-induced colitis patients were compared with those of UC patients. RESULTS: Anti-integrin αvß6 autoantibodies were found in 8/26 (30.8%) patients with ICI-induced colitis and 3/157 (1.9%) controls (P < 0.001). Patients with anti-integrin αvß6 autoantibodies had significantly more typical UC endoscopic features than those without the autoantibodies (P < 0.001). Anti-integrin αvß6 autoantibodies in ICI-induced colitis patients were associated with grade ≥3 colitis (P = 0.001) and steroid resistance (P = 0.005). Anti-integrin αvß6 autoantibody titers correlated with ICI-induced colitis disease activity. Anti-integrin αvß6 autoantibodies of ICI-induced colitis exhibited similar characteristics to those of UC. CONCLUSIONS: Anti-integrin αvß6 autoantibodies may serve as potential biomarkers for the diagnosis, classification, risk management, and monitoring the disease activity, of ICI-induced colitis.

Hepatic abscess induced by gastric cancer mimicking differentiated hepatocellular carcinoma.

A 58-year-old man was referred to our hospital with right abdominal pain. Contrast-enhanced computed tomography (CECT) showed a rim-enhanced lesion with a fluid collection in the right hepatic lobe. Upper gastrointestinal endoscopy revealed a Borrmann type 1 tumor on the middle gastric body, identified as an adenocarcinoma on pathology. The patient underwent percutaneous transhepatic abscess drainage and was treated with antibiotics. Two weeks after drainage, CECT revealed shrinkage of the abscess; however, the wall showed contrast enhancement. Needle biopsy was performed for the liver tumor, and it suggested the possibility of highly differentiated hepatocellular carcinoma. The patient first underwent gastrectomy, and the liver tumor was followed with CECT. Two months after surgery, CECT revealed that the liver tumor had vanished. Liver abscesses and infectious tumors can be difficult to differentiate between; therefore, careful scrutiny is essential before treatment.

The Safety and Clinical Validity of Endoscopic Submucosal Dissection for Early Gastric Cancer in Patients Aged More Than 85 Years.

Endoscopic submucosal dissection (ESD) is a safe and minimally invasive method for the treatment of early gastric cancer (EGC). However, whether ESD for EGC is also safe and feasible in patients aged ≥85 years is unclear. The patients enrolled in this study were divided into three groups: age ≥85 years (44 patients, 49 lesions), age 65−84 years (624 patients, 687 lesions), and age ≤64 years (162 patients, 174 lesions). We evaluated the incidence of adverse events (AEs) and overall survival (OS) and disease-specific survival (DSS). We analyzed the factors that had a significant impact on the prognosis of patients aged ≥85 years. No significant differences were found in the incidence of AEs among the three groups (p = 0.612). The OS was significantly lower in patients aged ≥85 years (p < 0.001). Conversely, DSS was not significantly worse in patients aged ≥85 years (p = 0.100). The poor Geriatric Nutritional Risk Index correlated with poor prognosis in patients aged ≥85 years (p < 0.001). ESD is a safe and valid treatment for EGC in patients aged ≥85 years. However, the indications should be carefully decided because it is difficult to estimate the survival contribution of ESD for EGC in patients aged ≥85 years, especially in those with poor nutritional status.

Clinical impact of a novel device delivery system in the diagnosis of bile duct lesions: A single-center experience.

BACKGROUND AND AIM: Pathological evaluation is essential for the diagnosis of biliary tract diseases. However, existing evaluation methods have various challenges in terms of operability and diagnostic performance. The present study aimed to evaluate the feasibility, utility, and safety of a novel device delivery system for bile duct biopsy. METHODS: This study was conducted as a retrospective, descriptive analysis at a single center. Overall, 25 examinations in 14 consecutive patients who underwent transpapillary biopsies for biliary lesions using the novel device delivery system from July to November 2020 were reviewed. Number and time of biopsy, technical success rate, adequate tissue sampling rate, adverse events, and diagnostic performance of bile duct biopsies using the novel device were evaluated. Moreover, negative surgical margins were assessed in patients who underwent surgical resection after mapping biopsy. RESULTS: The median number of biopsy samples was five (range: 2-13), with a median biopsy time of 11.6 min. The technical success rate was 100% (140/140), with an adequate sampling rate of 82.9% (116/140). These rates did not differ depending on the biopsy site or purpose. There were no serious adverse events related to the procedures. The diagnostic sensitivity, specificity, and accuracy of biliary stricture were 90%, 100%, and 92.3%, respectively. Negative surgical margins were confirmed in all patients undergoing surgical resection, including one patient with a surgical procedure changed based on the results of mapping biopsy. CONCLUSIONS: The novel device delivery system has potentials in diagnosing biliary tract diseases and determining appropriate treatment strategies.

Essential role of Notch/Hes1 signaling in postnatal pancreatic exocrine development.

BACKGROUND: Notch/Hes1 signaling has been shown to play a role in determining the fate of pancreatic progenitor cells. However, its function in postnatal pancreatic maturation is not fully elucidated. METHODS: We generated conditional Hes1 knockout and/or Notch intracellular domain (NICD) overexpression mice in Ptf1a- or Pdx1-positive pancreatic progenitor cells and analyzed pancreatic tissues. RESULTS: Both Ptf1acre/+; Hes1f/f and Ptf1acre/+; Rosa26NICD mice showed normal pancreatic development at P0. However, exocrine tissue of the pancreatic tail in Ptf1acre/+; Hes1f/f mice atrophied and was replaced by fat tissue by 4 weeks of age, with increased apoptotic cells and fewer centroacinar cells. This impaired exocrine development was completely rescued by NICD overexpression in Ptf1acre/+; Hes1f/f; Rosa26NICD mice, suggesting compensation by a Notch signaling pathway other than Hes1. Conversely, Pdx1-Cre; Hes1f/f mice showed impaired postnatal exocrine development in both the pancreatic head and tail, revealing that the timing and distribution of embryonic Hes1 expression affects postnatal exocrine tissue development. CONCLUSIONS: Notch signaling has an essential role in pancreatic progenitor cells for the postnatal maturation of exocrine tissue, partly through the formation of centroacinar cells.