Cancer is the leading cause of death in the world. Development of minimally invasive biomarkers for early detection of cancer is urgently needed to reduce high morbidity and mortality associated with malignancy. MicroRNAs (miRNAs) are small regulatory RNAs that modulate the activity of specific mRNA targets and play important roles in a wide range of physiologic and pathologic processes. Recently, miRNAs were found to be dysregulated in a variety of diseases including cancer. Emerging evidence suggests that miRNAs are involved in tumor initiation and progression. Together, the different expression profiles of miRNAs in cancer, and the stability of circulating miRNAs, make them new potentially clinical biomarkers for cancer diagnosis, classification, therapeutic decisions, and prognosis.

Cholangiocarcinoma (CCA) is a fatal disease without effective targeted therapy. We screened a small-molecule library of 116 inhibitors targeting different targets of the cell cycle and discovered several kinases, including Cyclin-dependent kinase 7 (CDK7) as vulnerabilities in CCA. Analysis of multiple CCA data sets demonstrated that CDK7 was overexpressed in CCA tissues. Further studies demonstrated that CDK7 inhibitor THZ1 inhibited cell viability and induced apoptosis in CCA cells. We also showed that THZ1 inhibited CCA cell growth in a xenograft model. RNA-sequencing followed by Gene ontology analysis showed a striking impact of THZ1 on DNA-templated transcriptional programs. THZ1 downregulated CDK7-mediated phosphorylation of RNA polymerase II, indicative of transcriptional inhibition. A number of oncogenic transcription factors and survival proteins, like MCL1, FOSL1, and RUNX1, were repressed by THZ1. MCL1, one of the antiapoptotic BCL2 family members, was significantly inhibited upon THZ1 treatment. Accordingly, combining THZ1 with a BCL2/BCL-XL inhibitor ABT-263 synergized in impairing cell growth and driving apoptosis. Our results demonstrate CDK7 as a potential target in treating CCA. Combinations of CDK7 inhibition and BCL2/BCL-XL inhibition may offer a novel therapeutic strategy for CCA.

The risk factors for post-ERCP cholecystitis (PEC) have not been characterized. Hence, this study aimed to identify the potential risk factors for PEC. The medical records of 4238 patients undergoing the first ERCP in a single center from January 2012 to December 2016 were analyzed in this study. A multivariate analysis was used to identify the risk factors. This study included 2672 patients who met the enrollment criteria. Of these, 36 patients (incidence rate of 1.35%) developed PEC within 2 weeks of the procedure. Univariate and multivariate analyses identified the following factors associated with PEC: history of acute pancreatitis [odds ratio (OR) = 2.60; 95% confidence interval (CI): 1.29–5.23], history of chronic cholecystitis (OR = 8.47; 95% CI: 2.54–28.24), gallbladder opacification (OR = 2.79; 95% CI: 1.37–5.70), biliary duct metallic stent placement (OR = 3.66; 95% CI: 1.78–7.54), and high leukocyte count before ERCP (OR = 1.10; 95% CI: 1.04–1.17). The prediction model incorporating these factors demonstrated an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.80–0.91). A prognostic nomogram was developed using the aforementioned variables to estimate the probability of PEC. The risk factors, including the history of acute pancreatitis, history of chronic cholecystitis, gallbladder opacification, biliary duct metallic stent placement, and high leucocyte counts before ERCP, increased the occurrence of PEC and were positive predictors for PEC. The constructed nomogram was used to estimate the risk of PEC, guiding the implementation of prophylactic measures to prevent PEC in clinical practice.

Cholangiocarcinoma (CCA), a devastating neoplasm, is highly resistant to current chemotherapies. CCA cells frequently overexpress the antiapoptotic protein myeloid cell leukemia-1(Mcl-1), which is responsible for its extraordinary ability to evade cell death. Triptolide, a bioactive ingredient extracted from Chinese medicinal plant, has been shown to inhibit cell proliferation and induce apoptosis in several cancers.

Endoscopic transpapillary cannulation of the gallbladder is useful but challenging. This study aimed to investigate cystic duct anatomy patterns, which may guide cystic duct cannulation. A total of 226 patients who underwent endoscopic transpapillary cannulation of the gallbladder were analyzed retrospectively. According to the cystic duct take-off, 226 cystic duct patterns were divided into 3 patterns: Type I (193, 85.4%), located on the right and angled up; Type II (7, 3.1%), located on the right and angled down; and Type III (26, 11.5%), located on the left and angled up. Type I was further divided into three subtypes: Line type, S type (S1, not surrounding the common bile duct; S2, surrounding the common bile duct), and α type (α1, forward α; α2, reverse α). Types I and III cystic ducts were easier to be cannulated with a higher success rate (85.1 and 86.4%, respectively) compared with Type II cystic duct (75%) despite no statistically significant difference. The reasons for the failure of gallbladder cannulation included invisible cyst duct take-off, severe cyst duct stenosis, impacted stones in cyst duct or neck of the gallbladder, sharply angled cyst duct, and markedly dilated cyst duct with the tortuous valves of Heister. Classification of cystic duct patterns was helpful in guiding endoscopic transpapillary gallbladder cannulation.

INTRODUCTION: A modified cap-assisted endoscopic mucosal resection (mEMR-C), introduced in this study, was a novel variation of the standard EMR. We aimed to compare the outcomes of mEMR-C and endoscopic submucosal dissection (ESD) for the treatment of small (≤20 mm) intraluminal gastric gastrointestinal stromal tumors (gGISTs). METHODS: This retrospective study included 43 patients who underwent mEMR-C and 156 patients who received ESD at Nanjing Drum Tower Hospital. Baseline characteristics, adverse events, and clinical outcomes were compared between the 2 groups. Univariate and multivariable analyses were conducted to adjust for confounders. After propensity score matching using sex, year, location, and tumor size, outcomes were compared with 41 patients in each group. RESULTS: A total of 199 patients underwent endoscopic resection and the en bloc resection rate was 100%. The complete resection rate was comparable in both groups (P = 1.000). Approximately 9.5% of all patients had a positive margin. There was no significant difference in positive margin for patients undergoing mEMR-C or ESD (9.3% vs 9.6%, P = 1.000). No difference in adverse events in both groups (P = 0.724). The mEMR-C was associated with shorter operation time and lower cost than the ESD. Recurrence was reported in 2 patients at 1 and 5 years after ESD during a median follow-up of 62 months. No metastasis and disease-related death were identified in both groups. Propensity score matching analysis revealed similar results. DISCUSSION: The mEMR-C was found to be the preferable technique for small (≤20 mm) intraluminal gGISTs with shorter operation time and lower cost as compared with ESD.