Correction to: Prognostic Factors in Overall Survival of Patients with Unresectable Intrahepatic Cholangiocarcinoma Treated by Means of Yttrium-90 Radioembolization: Results in Therapy-Naïve Patients.

The published article has an error in the first name initial of one of the authors. "M. Justinger" should be "C. Justinger" as shown in this erratum.

Prognostic Factors in Overall Survival of Patients with Unresectable Intrahepatic Cholangiocarcinoma Treated by Means of Yttrium-90 Radioembolization: Results in Therapy-Naïve Patients.

INTRODUCTION: To investigate prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) therapy-naïve patients after yttrium-90 (Y-90) radioembolization (RE) therapy. MATERIALS AND METHODS: Between 2005 and 2016, 21 patients with ICC were treated with Y-90 RE only and their survival data were analyzed. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULT: The overall median survival was 15 months. Survival was significantly (p = 0.009) prolonged in patients with tumor burden of ≤ 25% (n = 8, OS 37.5 months) versus those with a tumor burden of 25-50% (n = 13, OS 15 months). The other variables: tumor morphology (infiltrative vs. peripheral), tumor distribution (solitary vs. multifocal), lobes involved (unilobar vs. bilobar), FDG PET status (FDG avid vs. non-avid), RE treatment sessions (1 session vs. 2 sessions), metastases (metastasis vs. no metastasis) and RECIST criteria, had no significant impact on survival. CONCLUSION: Tumor burden represents a key prognostic factor of survival in therapy-naïve patients with unresectable ICC treated with Y-90 RE therapy only.

Improvement in 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd) concentration by 5-fluorouracil-polyethylene-glycol-liposomes in abdominal stop-flow: treatment of VX2 liver-tumor-bearing rabbits.

The application of liposome-encapsulated cytostatics results in higher concentrations in tumor tissue. This effect can be further increased by blood flow retardation with longer retention time in the tumor and by arterial administration. In abdominal stop-flow therapy, a separate partial circulation with a defined flow is realized via a roller pump under hypoxic conditions. Forty chinchilla rabbits with VX-2 liver tumors were treated either intra-aortally (stop-flow therapy) or systemically with 50 mg 5-FU or 5-FU-PEG liposomes. During therapy, pH and pO2 were measured at regular intervals. After 20 minutes, concentrations of 5-FU and its metabolite FdUrd were determined by HPLC in different organs and the liver tumor. Compared to the i.v. application of monosubstances, the combination of i.a. 5-FU-PEG liposomes and flow retardation increased the concentration in tumor tissue by a factor of 44 and even 100-fold in the para-aortal lymph nodes (LN). The concentration of 5-FU and FdUrd was increased by flow reduction, intraaortal application and liposomal encapsulation of 5-FU.

Intra-aortal therapy with 5-fluorouracil- polyethylene glycol stealth liposomes: does the metabolism of 5-fluorouracil into 5-fluoro-2'-deoxyuridine depend on ph value?. An animal study in VX-2 liver tumor-bearing rabbits.

BACKGROUND: The application of liposome-encapsulated cytostatics results in higher concentrations in tumor tissue. This effect can be further increased by blood flow retardation with longer retention time in the tumor and by arterial administration realized in abdominal stop-flow therapy, a separate partial circulation with a defined flow under hypoxic conditions. The pH changes under stop-flow therapy may affect the further metabolism of 5-fluorouracil (5-FU), used here. METHODS: The in vitro 5-fluoro-2'-deoxyuridine (5-FUrd) concentrations at increasing pH values were measured using liposomal encapsulated and free 5-FU. Subsequently, 20 chinchilla rabbits were treated intra-aortally with 5-FU or 5-FU-polyethylene glycol (PEG) liposomes. The pH value was maintained in the physiological range by continuous NaHCO3 application. After 20 min, concentrations of 5-FU and its metabolite 5-FUrd were determined in different organs, the perfusate, serum and the VX-2 tumor by HPLC. RESULTS: The in vitro 5-FUrd concentrations, which occur only in the physiological pH range, were doubled by the use of 5-FU-PEG liposomes. In the animal trial, NaHCO(3) titration doubled the 5-FUrd concentrations found in our preliminary studies. Compared to free 5-FU, 5-FU-PEG liposomes significantly increased the concentrations in the VX-2 liver tumor by 6.6-fold and in the para-aortal lymph nodes by 8.76-fold. CONCLUSION: The metabolism of 5-FU into its active metabolite 5-FUrd depends on the pH value and can be modulated. 5-FUrd concentrations can be approximately doubled with the intra-aortal application of 5-FU-PEG liposomes compared to free 5-FU.

Improved tumor targeting by regional carboplatin application combined with Gelfoam. An experimental study on liver tumor-bearing rabbits.

Regional chemotherapy of liver metastases is a promising alternative to systemic chemotherapy. Despite a number of theoretical advantages, extended life expectancy has only been confirmed in two studies. Since tumors have a concentration-dependent response to cytostatics, the primary goal is to increase the cytostatic concentration applied in tumor tissue. The aim of this study on liver tumor-bearing chinchilla rabbits was to show that the regional application of carboplatin leads to an increased concentration in tumor tissue. A further increase in carboplatin concentration by additional regional application of gelatine powder (Gelfoam) was demonstrated in a subsequent test; regional compared to intravenous application increased the carboplatin concentration in the tumor tissue by a factor of 12.1 and coapplication with Gelfoam increased the cytostatic concentration by a factor of 44.3.

Increased carboplatin concentration in liver tumors through temporary flow retardation with starch microspheres (Spherex) and gelatin powder (Gelfoam): an experimental study in liver tumor-bearing rabbits.

Regional chemotherapy of primary and secondary malignant liver tumors is superior to systemic therapy. The regional advantage can be further increased by flow retardation. Absorbable gelatin powder (Gelfoam) and starch microspheres (Spherex) may serve as embolizing agents because of their particle size and embolization time. Carboplatin was for the first time applied as a cytostatic agent in regional chemotherapy. Embolization and flow retardation times were measured. The embolization time of Gelfoam was 27 min, and that of starch microspheres (Spherex), 7 min, on average. Mean flow retardation of Gelfoam was 153 min, and that of starch microspheres (Spherex) 38 min. The concentration differences in systemic and regional chemotherapy were determined in VX-2 liver tumor-bearing rabbits. In regional chemotherapy, the tumor concentration was increased by a factor of 3.6 compared with systemic therapy. Coapplication with an embolizing agent increased the tumor concentration of carboplatin by a factor of 44 to 47. Concentrations of absorbable gelatin powder (Gelfoam) and starch microspheres (Spherex) did not differ significantly.