Evaluation of ERCP-related perforation: a single-center retrospective study.

Background: Endoscopic retrograde cholangiopancreatography (ERCP)-related perforation is a rare and serious adverse event. The aim of our study was to evaluate the risk factors and management of ERCP-related perforation, and to further determine the predictive factors associated with perforation outcome. Methods: A total of 27,018 ERCP procedures performed at the First Affiliated Hospital of Nanchang University (Nanchang, China) between January 2007 and March 2022 were included in the investigation of ERCP-related perforation. Medical records and endoscopic data were extracted to analyse the risk factors, management, and clinical outcome of ERCP-related perforation. Results: Seventy-six patients (0.28%) were identified as having experienced perforation following ERCP. Advanced age, Billroth II anatomy, precut sphincterotomy, and papillary balloon dilatation were significantly associated with ERCP-related perforation. Most patients with perforation (n = 65) were recognized immediately during ERCP whereas 11 were recognized later on. The delay in recognition primarily resulted from stent migration (n = 9). In addition, 12 patients experienced poor clinical outcome including death or hospice discharge (n = 3), ICU admission for >3 days (n = 6), and prolonged hospital stay for >1 month due to perforation (n = 3). Cancer and systemic inflammatory response syndrome (SIRS) are associated with a higher risk of poor outcome. Conclusions: Advanced age, Billroth II anatomy, precut sphincterotomy, and balloon dilation increase the risk of ERCP-related perforation whereas cancer and SIRS independently predicted poor clinical outcome.

The assessment of the ASGE-grading system of ERCP: a large-sample retrospective study.

BACKGROUND AND AIMS: The American Society for Gastrointestinal Endoscopy (ASGE) has developed a complexity-grading system for endoscopic retrograde cholangiopancreatography (ERCP) to predict technical success and adverse events. This study aimed to assess the association between the degree of difficulty for ERCP and the rates of success and adverse event, in turn demonstrating the validity and practicality of this system. METHODS: ERCP procedures performed in the First Affiliated Hospital of Nanchang University from January 2011 to December 2020 were retrospectively reviewed. Procedural success and adverse events were recorded based on difficulty level according to the ASGE-grading system. RESULTS: A total of 20,652 ERCP procedures performed during the study period were analyzed, including 1908 procedures considered grade 1(9.2%), 10,170 procedures considered grade 2 (49.2%), 7764 procedures considered grade 3 (37.6%), 810 procedures considered grade 4 (3.9%). The overall success rate increased from 92.8% in 2011-2015 to 94.0% in 2016-2020, while the distribution of procedures and the incidence of complications showed little variation. The success rate revealed a significantly decreasing trend with increasing difficulty (ranging from 55.6 to 98.6%), mainly for biliary diseases. In addition, the difficulty scale was not associated with any differences in the rate of adverse event, except for the pancreatitis for grade 1 procedures, which had a low incidence. CONCLUSIONS: The ASGE-grading system can help predict the success rate of ERCP procedures but showed poor performance in predicting adverse events. Further exploration may be required to improve the grading system by adjusting or including certain clinical parameters, and to validate the system for extrapolation to other endoscopy units.

Transcription factor FOXA3 promotes the development of Hepatoblastoma via regulating HNF1A, AFP, and ZFHX3 expression.

OBJECTIVE: In this research paper, we aimed to study the role of FOXA3 in hepatoblastoma (HB) and the molecular mechanism. METHODS: Immunohistochemistry was applied to determine the expression situation of FOXA3 and AFP in HB tissues and the adjacent normal tissues. FOXA3, HNF1A, and ZFHX3 expressions in HB tissues and the normal tissues were measured by Western blot. HB cell lines were randomly divided into 4 groups: Model, si-NC, si-FOXA3-1, and si-FOXA3-2 group. The HB cell viability and colony formation characteristics in the 4 groups were explored by CCK-8 and cell cloning formation assay, respectively. The expression of FOXA3, AFP, HNF1A, ZFHX3, and MYC in HB cells after knockdown of FOXA3 was measured. RESULTS: FOXA3, AFP, and HNF1A expressions were significantly up-regulated in HB tissues, while ZFHX3 expression was down-regulated. Knockdown of FOXA3 markedly inhibited HB cell viability and cloning formation ability. Knockdown of FOXA3 decreased FOXA3, AFP, and HNF1A/MYC expression, while increased ZFHX3 expression. CONCLUSION: FOXA3 promotes the occurrence and development of HB by up-regulating AFP and HNF1A/MYC expression, and down-regulating ZFHX3 expression.

Inhibition of P-glycoprotein and increasing of drug-sensitivity of a human carcinoma cell line (KB-A-1) by an antisense oligodeoxynucleotide-doxorubicin conjugate in vitro.

To improve the antisense activity of AS ODN (antisense oligodeoxynucleotide), a conjugate covalently linked to DOX (doxorubicin) at its 3'-end was synthesized and its antisense activity in human carcinoma DOX-resistant cells (KB-A-1) was investigated in vitro. The intracellular DOX concentration in KB-A-1 cells treated with the conjugate was detected in vitro by HPLC. Results showed that the intracellular DOX concentration was 6.4-fold higher in KB-A-1 cells treated with the conjugate when compared with that in the cells treated with DOX alone. In contrast, a 1.8-fold increase in the concentration of DOX was observed when the cells were treated with AS ODN. Reverse transcriptase PCR and Western-blot analysis showed a more significant decrease in the amount of mdr1 (multidrug resistance 1 gene) mRNA and P-glycoprotein in KB-A-1 cells. Chemosensitivity of KB-A-1 cells to DOX was also investigated in vitro. When the cells were first exposed to the conjugate (0.5 microM) for 24 h and then exposed to DOX for 24 h, the IC(50) value of DOX decreased from 21.5 to 2.2 microM, whereas the IC(50) value of DOX decreased only to 16.8 microM when the cells were treated with the mixture of the same concentration of AS ODN. These results suggest that the conjugate is effective in reversing multidrug resistance. Further studies will be conducted to explore the effect of the conjugate on tumours in vivo.

In vitro reversal MDR of human carcinoma cell line by an antisense oligodeoxynucleotide-doxorubicin conjugate.

A conjugate of antisense oligodeoxynucleotide (AS ODN) covalently linked with deoxorubicin (DOX) was synthesized. Its properties and antitumour activity in human carcinoma DOX resistant cells (KB-A-1) were investigated in vitro. The results showed that the conjugate was strongly stable both in Dulbecco's Phosphate-Buffered Saline (PBS) and in culture medium. The intracellular concentration of the conjugate was higher than that of the AS DON by HPLC analysis. The conjugate showed potent dose-dependent inhibition to the growth of KB-A-1 cells. Chemosensitivity of KB-A-1 cells to DOX was also investigated in vitro. When the cells were first exposed to the conjugate (0.5 microM) and then exposed to DOX for 24 h, the IC50 value of DOX decreased from 21.5 to 2.2 microM. In contrast, when treated with the mixture of the same concentration of the AS ODN with equivalent DOX, the IC50 value of DOX was 16.8 microM. Intracellular DOX concentration was detected in KB-A-1 treatment with the conjugate in vitro by HPLC. The results showed that the intracellular DOX concentration was 6.4-fold increased in KB-A-1 cells treated with the conjugate compared to treatment with DOX alone. In contrast, 1.8-fold increasing was observed when treated with the AS ODN. Western blot analysis showed a significantly decrease in the amount of P-glycoprotein in KB-A-1 cells. These results suggest that the conjugate is effective in reversing multidrug resistance. Certainly, further studies are conducting to explore the antitumour effect of the conjugate in vivo.