Purpose: Cholestatic complications remain a primary cause of post-liver transplantation (LTX) morbidity in pediatric patients. Standard biliary access by endoscopic retrograde cholangioscopy may not be feasible due to modified biliary drainage. Percutaneous transhepatic biliary drainage (PTCD) may be performed alternatively. However, systematic data concerning safety and efficacy of PTCD in these patients are scarce. Methods: In this retrospective study, procedural and safety characteristics of PTCD in pediatric patients following LTX were analyzed. We compared laboratory indicators of inflammation, cholestasis, and graft function before and at 6 and 12 months after the first PTCD insertion. Efficacy was analyzed by percentage of patients without cholangitis, need for surgical biliary re-intervention and re-transplantation during a follow-up period of 60 months. Results: Over a decade, PTCD was attempted in a total of 15 patients, with technical success (93.3%) in 14 patients. Periprocedural complications, including bleeding (7.1%) and cholangitis (21.4%) were observed in patients. During follow-up, both MELD-score (baseline:13 [8–15] vs. 12 months: 8 [7–8], p<0.001) and parameters of cholestasis (GGT: baseline: 286 [47–458] U/L vs. 12 months: 105 [26–147] U/L, p=0.024) decreased. Prior to PTCD, cholangitis (64.3%) and cholangiosepsis (21.4%) were common complications. In contrast, following PTCD, cholangitis occurred in only one patient (7.1%). Five patients (35.7%) needed surgical biliary re-intervention and two (14.3%) required re-transplantation. Conclusion PTCD in pediatric patients following LTX had an acceptable safety profile, demonstrating a biochemical improvement of both cholestasis and graft function and may prevent cholestatic complications, thus reducing the need for surgical re-intervention and re-transplantation.

Purpose: Cholestatic complications remain a primary cause of post-liver transplantation (LTX) morbidity in pediatric patients. Standard biliary access by endoscopic retrograde cholangioscopy may not be feasible due to modified biliary drainage. Percutaneous transhepatic biliary drainage (PTCD) may be performed alternatively. However, systematic data concerning safety and efficacy of PTCD in these patients are scarce. Methods: In this retrospective study, procedural and safety characteristics of PTCD in pediatric patients following LTX were analyzed. We compared laboratory indicators of inflammation, cholestasis, and graft function before and at 6 and 12 months after the first PTCD insertion. Efficacy was analyzed by percentage of patients without cholangitis, need for surgical biliary re-intervention and re-transplantation during a follow-up period of 60 months. Results: Over a decade, PTCD was attempted in a total of 15 patients, with technical success (93.3%) in 14 patients. Periprocedural complications, including bleeding (7.1%) and cholangitis (21.4%) were observed in patients. During follow-up, both MELD-score (baseline:13 [8–15] vs. 12 months: 8 [7–8], p<0.001) and parameters of cholestasis (GGT: baseline: 286 [47–458] U/L vs. 12 months: 105 [26–147] U/L, p=0.024) decreased. Prior to PTCD, cholangitis (64.3%) and cholangiosepsis (21.4%) were common complications. In contrast, following PTCD, cholangitis occurred in only one patient (7.1%). Five patients (35.7%) needed surgical biliary re-intervention and two (14.3%) required re-transplantation. Conclusion PTCD in pediatric patients following LTX had an acceptable safety profile, demonstrating a biochemical improvement of both cholestasis and graft function and may prevent cholestatic complications, thus reducing the need for surgical re-intervention and re-transplantation.

Purpose: Cholestatic complications remain a primary cause of post-liver transplantation (LTX) morbidity in pediatric patients. Standard biliary access by endoscopic retrograde cholangioscopy may not be feasible due to modified biliary drainage. Percutaneous transhepatic biliary drainage (PTCD) may be performed alternatively. However, systematic data concerning safety and efficacy of PTCD in these patients are scarce. Methods: In this retrospective study, procedural and safety characteristics of PTCD in pediatric patients following LTX were analyzed. We compared laboratory indicators of inflammation, cholestasis, and graft function before and at 6 and 12 months after the first PTCD insertion. Efficacy was analyzed by percentage of patients without cholangitis, need for surgical biliary re-intervention and re-transplantation during a follow-up period of 60 months. Results: Over a decade, PTCD was attempted in a total of 15 patients, with technical success (93.3%) in 14 patients. Periprocedural complications, including bleeding (7.1%) and cholangitis (21.4%) were observed in patients. During follow-up, both MELD-score (baseline:13 [8–15] vs. 12 months: 8 [7–8], p<0.001) and parameters of cholestasis (GGT: baseline: 286 [47–458] U/L vs. 12 months: 105 [26–147] U/L, p=0.024) decreased. Prior to PTCD, cholangitis (64.3%) and cholangiosepsis (21.4%) were common complications. In contrast, following PTCD, cholangitis occurred in only one patient (7.1%). Five patients (35.7%) needed surgical biliary re-intervention and two (14.3%) required re-transplantation. Conclusion PTCD in pediatric patients following LTX had an acceptable safety profile, demonstrating a biochemical improvement of both cholestasis and graft function and may prevent cholestatic complications, thus reducing the need for surgical re-intervention and re-transplantation.

Purpose: Cholestatic complications remain a primary cause of post-liver transplantation (LTX) morbidity in pediatric patients. Standard biliary access by endoscopic retrograde cholangioscopy may not be feasible due to modified biliary drainage. Percutaneous transhepatic biliary drainage (PTCD) may be performed alternatively. However, systematic data concerning safety and efficacy of PTCD in these patients are scarce. Methods: In this retrospective study, procedural and safety characteristics of PTCD in pediatric patients following LTX were analyzed. We compared laboratory indicators of inflammation, cholestasis, and graft function before and at 6 and 12 months after the first PTCD insertion. Efficacy was analyzed by percentage of patients without cholangitis, need for surgical biliary re-intervention and re-transplantation during a follow-up period of 60 months. Results: Over a decade, PTCD was attempted in a total of 15 patients, with technical success (93.3%) in 14 patients. Periprocedural complications, including bleeding (7.1%) and cholangitis (21.4%) were observed in patients. During follow-up, both MELD-score (baseline:13 [8–15] vs. 12 months: 8 [7–8], p<0.001) and parameters of cholestasis (GGT: baseline: 286 [47–458] U/L vs. 12 months: 105 [26–147] U/L, p=0.024) decreased. Prior to PTCD, cholangitis (64.3%) and cholangiosepsis (21.4%) were common complications. In contrast, following PTCD, cholangitis occurred in only one patient (7.1%). Five patients (35.7%) needed surgical biliary re-intervention and two (14.3%) required re-transplantation. Conclusion PTCD in pediatric patients following LTX had an acceptable safety profile, demonstrating a biochemical improvement of both cholestasis and graft function and may prevent cholestatic complications, thus reducing the need for surgical re-intervention and re-transplantation.

Purpose: Cholestatic complications remain a primary cause of post-liver transplantation (LTX) morbidity in pediatric patients. Standard biliary access by endoscopic retrograde cholangioscopy may not be feasible due to modified biliary drainage. Percutaneous transhepatic biliary drainage (PTCD) may be performed alternatively. However, systematic data concerning safety and efficacy of PTCD in these patients are scarce. Methods: In this retrospective study, procedural and safety characteristics of PTCD in pediatric patients following LTX were analyzed. We compared laboratory indicators of inflammation, cholestasis, and graft function before and at 6 and 12 months after the first PTCD insertion. Efficacy was analyzed by percentage of patients without cholangitis, need for surgical biliary re-intervention and re-transplantation during a follow-up period of 60 months. Results: Over a decade, PTCD was attempted in a total of 15 patients, with technical success (93.3%) in 14 patients. Periprocedural complications, including bleeding (7.1%) and cholangitis (21.4%) were observed in patients. During follow-up, both MELD-score (baseline:13 [8–15] vs. 12 months: 8 [7–8], p<0.001) and parameters of cholestasis (GGT: baseline: 286 [47–458] U/L vs. 12 months: 105 [26–147] U/L, p=0.024) decreased. Prior to PTCD, cholangitis (64.3%) and cholangiosepsis (21.4%) were common complications. In contrast, following PTCD, cholangitis occurred in only one patient (7.1%). Five patients (35.7%) needed surgical biliary re-intervention and two (14.3%) required re-transplantation. Conclusion PTCD in pediatric patients following LTX had an acceptable safety profile, demonstrating a biochemical improvement of both cholestasis and graft function and may prevent cholestatic complications, thus reducing the need for surgical re-intervention and re-transplantation.

Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T-acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with 10 μM up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to 1.94 μM. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.
Apoptosis ; Biological Products ; Erythrocytes ; Hemolysis ; Humans ; Inhibitory Concentration 50 ; Leukocytes ; Phosphotransferases ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Protein Kinases ; Quinazolinones