Peroral Cholangioscopy-Guided Targeted Biopsy versus Conventional Endoscopic Transpapillary Forceps Biopsy for Biliary Stricture with Suspected Bile Duct Cancer

Background: The recent improvement of peroral cholangioscopy (POCS) maneuverability has enabled the precise, targeted biopsy of bile duct lesions under direct cholangioscopic vision. However, as only small-cup biopsy forceps can pass through the scope channel, the resulting small sample size may limit the pathological diagnosis of biopsy specimens. This study compared the diagnostic abilities of POCS-guided biopsy and conventional fluoroscopy-guided biopsy for bile duct cancer. Method: This multicenter, retrospective cohort study included patients exhibiting bile duct stricture with suspected cholangiocarcinoma in whom POCS-guided and fluoroscopy-guided biopsies were performed in the same session. The primary endpoint was the diagnostic sensitivity for malignancy. The size and quality of the biopsy specimens were also compared. Result: A total of 59 patients were enrolled. The sensitivity of POCS-guided biopsy was similar to that of fluoroscopy-guided biopsy (54.0% and 64.0%, respectively). However, when the modalities were combined, the sensitivity increased to 80.0%. The mean specimen size from POCS-guided biopsy was significantly smaller than that from fluoroscopy-guided biopsy. The specimen quality using fluoroscopy-guided biopsy was also better than that using POCS-guided biopsy. Conclusions: The diagnostic sensitivity of POCS-guided biopsy is still insufficient, mainly because of the limited specimen quantity and quality. Therefore, conventional fluoroscopy-guided biopsy would be helpful to improve diagnostic sensitivity.

Intraductal Papillary Mucinous Neoplasm of the Pancreas: Need for a Tailored Approach to a Rare Entity

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a relatively new entity that has gained increased attention because of its unique features – presence of different subtypes with different malignant potential, biological behavior, and prognosis, higher rates of recurrences and concomitant or metachronous pancreatic duct cancer. It is rare with an incidence of 4 to 5 cases per 100 000. The relative lack of experience significantly hampers decision making for surgery (pancreatic head resection, distal pancreatectomy or enucleation) or follow-up. Herein we present two cases managed by diametrically different tactic according to the risk stratification – distal pancreatectomy with splenectomy and observation, respectively. An up-to-date literature review on the key points in diagnostics, indications for surgery, the extent of surgery, follow-up, and prognosis is provided. The tailored approach based on risk stratification is the cornerstone of management. Absolute indications for surgery are the lesions with high-risk stigmata, whereas the worrisome features should be evaluated by endoscopic ultrasound and fine-needle aspiration. Main duct and mixed type are usually referred to surgery, whereas the management of a branch type is more conservative due to the lower rate of invasive cancer. Strict postoperative follow-up is mandatory even in negative resection margins due to a high risk for recurrences and metachronous lesions. Despite the guidelines, the intraductal papillary mucinous neoplasm remains a major challenge for clinicians and surgeons in the balance the risk/benefit of observation versus resection. Risk stratification plays a key role in decision-making. Future trials need to determine the optimal period of surveillance and the most reliable predictive factors for concomitant pancreatic duct cancer.

Pattern Recognition of microRNA Expression in Body Fluids using Nanopore Decoding at Sub-femtomolar Concentration

This paper describes nanopore decoding for microRNA (miRNA) expression patterns using DNA computing technology. miRNAs have shown promise as markers for cancer diagnosis due to their cancer type-specificity, and therefore simple strategies for miRNA-pattern recognition are required. We propose a system for pattern recognition of five types of miRNAs overexpressed in bile duct cancer (BDC). The information of miRNAs from BDC is encoded in diagnostic DNAs (dgDNAs) and decoded electrically by nanopore measurement. With this system, we succeeded in distinguishing miRNA expression patterns in the plasma of BDC patients using a label-free method and in real-time. Moreover, our dgDNA-miRNAs complexes can be captured by the nanopore at ultralow concentration, such as 0.1 fM. Such nanopore decoding with dgDNAs could be applied as a simple and early diagnostic tool for cancer in the future.

Pattern Recognition of microRNA Expression in Body Fluids using Nanopore Decoding at Sub-femtomolar Concentration

This paper describes nanopore decoding for microRNA (miRNA) expression patterns using DNA computing technology. miRNAs have shown promise as markers for cancer diagnosis due to their cancer type-specificity, and therefore simple strategies for miRNA-pattern recognition are required. We propose a system for pattern recognition of five types of miRNAs overexpressed in bile duct cancer (BDC). The information of miRNAs from BDC is encoded in diagnostic DNAs (dgDNAs) and decoded electrically by nanopore measurement. With this system, we succeeded in distinguishing miRNA expression patterns in the plasma of BDC patients using a label-free method and in real-time. Moreover, our dgDNA-miRNAs complexes can be captured by the nanopore at ultralow concentration, such as 0.1 fM. Such nanopore decoding with dgDNAs could be applied as a simple and early diagnostic tool for cancer in the future.

Cutting Edge Research for Exploration of Biomolecules for Gemcitabine-Based Chemo-Resistant Advanced Bile Duct Cancer: From Basic Study to Clinical Trial

Bile duct cancer (BDC) has been identified as a highly aggressive cancer arising from epithelial cells of the bile duct, including intrahepatic, perihilar, and extrahepatic [...]

Pharmacophore Based Design Of Probable Fgfr-1 Inhibitors From The 3d Crystal Structure Of Infigratinib - A Drug Used In The Treatment Of Cholangiocarcinomas

Background: Pemigatinib (INCB054828) and Infigratinib (BGJ398) are the few selective drugs that are approved by the FDA to treat cholangiocarcinoma, a rare form of bile duct cancer. Infigratinib is a pan FGFR inhibitor and has been found promising in Phase-3, first-line PROOF clinical trial. So, screening drug-like compounds having similar pharmacophoric features like infigratinib is the inspiration of the present work. Objective: The objective was to identify drug-like compounds with similar pharmacophoric features as in infigratinib. The compounds screened through the 3D query pharmacophore of infigratinib were also predicted for ADMET properties so that the compounds may have good bioavailability. Method: A pharmacophore was generated from the crystal structure of infigratinib with several pharmacophoric features such as hydrogen bond donor, hydrophobic, positive ionizable, and ring aromatic. MayBridge database containing 65,263 compounds was used for virtual screening (VS) using LibDock. The initial Hit compounds were subjected to ADMET predictions. Finally, two Hit compounds were selected and docked with the FGFR-1 receptor to predict the interaction of the ligand atoms with the amino acid residues of the receptor's active site. Result: The fit score for infigratinib, N-(4-fluorophenyl)-2-(5-((2-(4-methoxy-2,5-dimethylphenyl)-2-oxoethyl)thio)-4-methyl-4H-1,2,4-triazol-3-yl)acetamide (Hit-1) and 4-(4-((2-(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)ethyl)carbamoyl)pyridin-2-yl)-1-methylpiperazin-1-ium (Hit-4) is 4.58901, 4.36649, and 3.71732, respectively. The LibDock score of infigratinib, Hit-1, and Hit-4 is 122.474, 123.289, and 123.353, respectively. The binding affinity score (-PLP1) of infigratinib, Hit-1, and Hit-4 is -143.19, -102.72, and -91.71. Conclusion: The present study concluded that the two compounds designated as Hit-1 and Hit-4 have been identified as binders of FGFR-1, and Hit-4 occupies the whole pharmacophoric space of infigratinib, and both the compounds LibDock scores are better than the infigratinib. Other: The two compounds Hit-1 and Hit-4 may be synthesized and studied for their enzyme inhibition assay on FGFR-1 and biologically evaluated on different cell lines for Cholangiocarcinoma.