The adherence to the American Association for the Study of Liver Diseases 2018 guidelines in the management of hepatocellular carcinoma and its impact on survival.

Introduction: In two Korean and Italian studies, the adherence rate (AR) to ASSLD 2005 guidelines in the management of hepatocellular carcinoma (HCC) was 60%. In a US study, the AR to American Association for the Study of Liver Disease (AASLD) 2005 guidelines was 73.3%, 26.8%, 25.3%, and 58.8% for patients with Barcelona Clinic Liver Cancer (BCLC) Stage A, B, C, and D, respectively, and nonadherence to guidelines was associated with longer overall survival (OS) in patients with BCLC Stage D. Here, we explored the AR to AASLD 2018 guidelines and its impact on OS. Methods: Between 2017 and 2019, 148 unique treatment-naïve patients with HCC were identified. Patients were staged according to the BCLC staging system and their AR to AASLD 2018 guidelines was noted. OS was estimated using Kaplan-Meier method. Survivals among patients from different groups was compared using Log-rank test. Results: The overall AR to AASLD 2018 guidelines was 83%. The AR for BCLC Stages 0, A, B, C, and D were 100%, 97%, 77%, 77%, and 38%, respectively. In patients with BCLC Stage D, the OS of patients treated with modalities adherent versus nonadherent to AASLD 2018 guidelines was 0.03 vs. 5.2 months (P = 0.0005). Otherwise, adherence versus nonadherence to AASLD 2018 guidelines showed no statistically significant differences in OS for patients with BCLC Stages 0, A, B, and C. Conclusion: The overall AR to AASLD 2018 guidelines was 83%. Nonadherence to AASLD 2018 guidelines in patients with BCLC Stage D translated into better OS.

Epidermal growth factor receptor-activating mutation(E746_T751>VP) in pancreatic ductal adenocarcinoma responds to erlotinib, followed by epidermal growth factor receptor resistance-mediating mutation (A647T): A case report and literature review.

Despite recent advances in treatment with multidrug chemotherapy regimens, outcomes of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remain very poor. Treatment with targeted therapies has shown marginal benefits due to intrinsic or acquired resistance. Actionable mutations, while detected infrequently in patients with PDAC, are becoming increasingly used in personalized medicine. Here, we describe an epidermal growth factor receptor (EGFR)-activating mutation (E746_T751>VP) to erlotinib, a first-generation tyrosine kinase inhibitor (TKI), in a patient with metastatic PDAC. After an initial partial response to erlotinib for 12 months, the patient's disease progressed with emergence of the EGFR A647T mutation. Certainly, the patient also progressed after switching therapy to a third-generation EGFR TKI (osimertinib). This case illustrates the posttreatment evolution of EGFR A647T-mediated resistance to the first- and third-generation TKIs. To our knowledge, this is the first case to report the aforementioned activating and resistance-mediated mutations. In summary, genomic analysis performed in this patient with PDAC on the tumor biopsy and peripheral blood provided tools to understand mechanisms of response and resistance to targeted therapy with EFGR TKIs.

The Light at the End of the Tunnel.

Approximately 5%-10% of common bile duct (CBD) stones cannot be removed by conventional methods because of altered anatomy. Percutaneous transhepatic cholangioscopic lithotomy has been cited as a viable alternative. A 69-year-old woman with a history of Roux-en-Y was found to have a lesion obstructing the CBD. A cholangioscope was advanced through a percutaneous transhepatic sheath and demonstrated an obstructing stone in the CBD that was removed with lithotripsy. The rate of successful stone removal with percutaneous transhepatic cholangioscopic lithotomy is 90%, with complication rates similar to endoscopic retrograde cholangiopancreatography and is an option in patients with altered surgical anatomy.

Remote asymmetric induction about a crowded aromatic core.

Described are among the first highly diastereoselective, one-pot organometallic addition and hydride reduction reactions (>95% de) involving three symmetry-equivalent carbonyl centers, each that bears a 1,5-relationship to its nearest neighbor. Three-fold methyllithium addition to 2,4,6-trimethoxybenzene-1,3,5-tricarbaldehyde gives the anti,syn triol exclusively (by 1H NMR); addition of HMPA to the reaction or replacement of the substrate's methoxy groups with ethyl groups affords a statistical 3:1 (anti,syn:syn,syn) diastereomeric product ratio. Analogous asymmetric induction is found upon hydride reduction (using LiAlH4 or NaBH4) of the complementary triketone, 2,4,6-trimethoxybenzene-1,3,5-triethanone. Chelation and steric (gearing) effects about the crowded aromatic core contribute to the observed stereoselectivity.

Enhanced small-molecule assembly through directional intramolecular forces.

[reaction: see text] Directional intramolecular interactions play a critical role in the self-assembly of donor-sigma-acceptor molecules in solution. Amide functions on the periphery of the tricyclic core stabilize a C3-symmetric monomer conformation by intramolecular hydrogen bonding and dipole-dipole interactions. The molecules are effective organogelators and show long-range ordering in the bulk.