Impact of Neoadjuvant Chemotherapy on Hypertrophy of the Future Liver Remnant after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been demonstrated as a feasible procedure in extended liver resections as a means of successfully increasing the volume of the future liver remnant (FLR). Neoadjuvant chemotherapy (CTx) is toxic to the organ and may impair hepatic regeneration. This study was performed to assess the procedure's effect on hypertrophy of the FLR, including the short-term survival. STUDY DESIGN: We analyzed 19 consecutive ALPPS patients, of whom 58% (n = 11) received neoadjuvant CTx because of colorectal liver metastasis (CRM). Patients presented with multifocal CRM (n = 11, 58%); cholangiocarcinoma (n = 7, 37%), of which 5 were in the Klatskin position; and gallbladder carcinoma (n = 1, 5%). Hepatectomy was performed within 6 to 13 days after hepatic partition. Volumetry was performed before both liver partitioning and hepatectomy. A survival analysis was performed. RESULTS: Liver partition and portal vein ligation induced sufficient hypertrophy of the FLR, with an increased volume of 74% ± 35%. Patients underwent hepatectomy after a median of 8 days; in all cases R0 resection was achieved. Neoadjuvant CTx was shown to significantly impair hypertrophy. The volume of the FLR in non-CTx patients increased by 98% ± 35%; an increase of 59% ± 22% was observed in patients who underwent CTx (p = 0.027). Chemotherapy did not have an impact on either morbidity or in-hospital mortality, which were 68% and 16%, respectively. One-year overall survival was 53%, with a 1-year survival of 67% in CRM patients and 38% in non-CRM patients (p > 0.05). CONCLUSIONS: Data presented here demonstrate for the first time that neoadjuvant CTx significantly impairs hypertrophy of the FLR after ALPPS.

Effect of delayed CNI-based immunosuppression with Advagraf® on liver function after MELD-based liver transplantation [IMUTECT].

BACKGROUND: MELD-based allocation for liver transplantation follows the "sickest-patient-first" strategy. The latter patients present with both, decreased immune competence and poor kidney function which is further impaired by immunosuppressants. METHODS/DESIGN: In this prospective observational study, 50 patients with de novo low-dose standard Advagraf®-based immunosuppression consisting of Advagraf®, Mycophenolat-mofetil and Corticosteroids after liver transplantation will be evaluated. Advagraf® trough levels of 7-10 µg/l will be reached at the end of the first postoperative week. Immunostatus, infectious complications, graft and kidney function are compared between patients with a pretransplant calculated MELD-score of ≤20 and >20. Each group comprises of 25 consecutive patients. Prior to liver transplantation and on the postoperative days 1, 3 and 7, the patients' graft function (LiMAx test) will be evaluated. On the postoperative days 3, 5 and 7 the patients' immune status will be evaluated by the measurement of their monocytic HLA-DR status.Infectious complications (CMV-reactivation, wound infection, urinary tract infection, and pneumonia), graft- and kidney function will be analysed on day 0, within the first week, and 1, 3, 6, 9 and 12 months after liver transplantation. DISCUSSION: This study was designed to assess the effect of a standard low-dose Calcineurin inhibitor-based immunosuppression regime with Advagraf® on the rate of infectious complications, graft and renal function after liver transplantation. TRIAL REGISTRATION: The trial is registered at "Clinical Trials" (http://www.clinicaltrials.gov), NCT01781195.