Eosinophilic cholangitis: A case report of diagnostically challenging eosinophilic infiltrative biliary obstruction.

BACKGROUND: Evaluation of biliary strictures primarily focuses on ruling out malignancy in older age groups. With endoscopic tools such as endoscopic ultrasound (EUS) and cholangioscopy, improved biliary visualization has enhanced the investigation of intraluminal biliary lesions and provided modalities for targeted biopsies. Benign biliary strictures, however, may pose a diagnostic dilemma. CASE SUMMARY: A 71-year-old female with past medial history of hypothyroidism presenting for abnormal biliary imaging. Patients previous evaluation was concerning for common bile duct dilation with cholelithiasis, for which she underwent a cholecystectomy. Due to persistent symptoms and worsening liver function tests, she presented to our institution for further workup. Subsequently, the patient underwent an EUS and multiple ERCPs with cholangioscopy; biliary biopsies revealed no evidence of malignancy but concerning for prominent eosinophilic infiltration. After further review of multiple pathology specimens and the benign clinical course, we diagnosed the patient with eosinophilic cholangitis. CONCLUSION: Eosinophilic cholangitis is a rare disease and can present as a challenging case diagnostically. This case raises the potential utility of quantitative eosinophilic infiltration reporting in creating an objective diagnostic metric for eosinophilic cholangitis

A general approach to high-yield biosynthesis of chimeric RNAs bearing various types of functional small RNAs for broad applications.

RNA research and therapy relies primarily on synthetic RNAs. We employed recombinant RNA technology toward large-scale production of pre-miRNA agents in bacteria, but found the majority of target RNAs were not or negligibly expressed. We thus developed a novel strategy to achieve consistent high-yield biosynthesis of chimeric RNAs carrying various small RNAs (e.g. miRNAs, siRNAs and RNA aptamers), which was based upon an optimal noncoding RNA scaffold (OnRS) derived from tRNA fusion pre-miR-34a (tRNA/mir-34a). Multi-milligrams of chimeric RNAs (e.g. OnRS/miR-124, OnRS/GFP-siRNA, OnRS/Neg (scrambled RNA) and OnRS/MGA (malachite green aptamer)) were readily obtained from 1 l bacterial culture. Deep sequencing analyses revealed that mature miR-124 and target GFP-siRNA were selectively released from chimeric RNAs in human cells. Consequently, OnRS/miR-124 was active in suppressing miR-124 target gene expression and controlling cellular processes, and OnRS/GFP-siRNA was effective in knocking down GFP mRNA levels and fluorescent intensity in ES-2/GFP cells and GFP-transgenic mice. Furthermore, the OnRS/MGA sensor offered a specific strong fluorescence upon binding MG, which was utilized as label-free substrate to accurately determine serum RNase activities in pancreatic cancer patients. These results demonstrate that OnRS-based bioengineering is a common, robust and versatile strategy to assemble various types of small RNAs for broad applications

Role of endoscopic ultrasound for pre-intervention evaluation in early esophageal cancer.

BACKGROUND: Endoscopic ultrasound (EUS) stands as an accurate imaging modality for esophageal cancer staging, however utilization of EUS in early-stage cancer management remains controversial. Identification of non-applicability of endoscopic interventions with deep muscular invasion with EUS in pre-intervention evaluation of early-stage esophageal cancer is compared to endoscopic and histologic indicators. AIM: To display the role of EUS in pre-intervention early esophageal cancer staging and how the index endoscopic features of invasive esophageal malignancy compare for prediction of depth of invasion and cancer management. METHODS: This was a retrospective study of patients who underwent pre-resection EUS after a diagnosis of esophageal cancer at a tertiary medical center from 2012 to 2022. Patient clinical data, initial esophagogastroduodenoscopy/biopsy, EUS, and final resection pathology reports were abstracted, and statistical analysis was conducted to assess the role of EUS in management decisions. RESULTS: Forty nine patients were identified for this study. EUS T stage was concordant with histological T stage in 75.5% of patients. In determining submucosal involvement (T1a vs T1b), EUS had a specificity of 85.0%, sensitivity of 53.9%, and accuracy of 72.7%. Endoscopic features of tumor size > 2 cm and the presence of esophageal ulceration were significantly associated with deep invasion of cancer on histology. EUS affected management from endoscopic mucosal resection/submucosal dissection to esophagectomy in 23.5% of patients without esophageal ulceration and 6.9% of patients with tumor size < 2 cm. In patients without both endoscopic findings, EUS identified deeper cancer and changed management in 4.8% (1/20) of cases. CONCLUSION: EUS was reasonably specific in ruling out submucosal invasion but had relatively poor sensitivity. Data validated endoscopic indicators suggested superficial cancers in the group with a tumor size < 2 cm and the lack of esophageal ulceration. In patients with these findings, EUS rarely identified a deep cancer that warranted a change in management

Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416

Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416