Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial.

Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open-label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6-12 ng/mL. The primary endpoint was the proportion of treated biopsy-proven acute rejection (tBPAR)-free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR-free (P = 0.09); composite endpoint-free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial.

The European Policy for Liver Allocation in Patients Affected by Hepatocellular Carcinoma.

The main goal of allocation system is to guarantee an equal access to the limited resource of liver grafts for every class of patients on the waiting list, balancing between the ethical principles of equity, utility, benefit, need, and fairness. The aim of this review was to analyze liver allocation policies among these organizations, focusing on HCC. The European area considered for this analysis included 6 macro-areas or countries, which are congregated from the same policy of liver sharing and allocation. By this definition, the 6 areas identified are: Centro Nazionale Trapianti (CNT) in Italy; Eurotransplant (Germany, the Netherlands, Belgium, Luxembourg, Austria, Hungary, Slovenia, and Croatia); Organizacion Nacional de Transplantes (ONT) in Spain; Etablissement francais des Greffes (EfG) in France; NHS Blood Transplant (NHSBT) in the United Kingdom and Ireland; Scandiatransplant (Sweden, Norway, Finland, Denmark, and Iceland); Romanian National Policy. Each identified area, as network for organ sharing in Europe, adopts a basic allocation system that consider a policy center oriented or patient oriented. Priorization of patients affected by HCC in the waiting list for deceased donors liver transplant worldwide is dominated by 2 main principles: urgency and utility. The main message of this review is the absence of a common organs allocation policy over the Eurpean countries. Despite that, long-term survival of the community of patients listed for transplant due to HCC results, however, highly acceptable in Europe and comparable to the long-term survial reported in the UNOS register.

Repeat Hepatectomy for Recurrent Colorectal Liver Metastases: Is it Worth the Challenge?

INTRODUCTION: Repeat hepatectomy (RH) is considered a valuable option for management of recurrent colorectal liver metastases (R-CLM). Here, the outcome of RH for R-CLM was compared to that of patients who underwent single hepatectomy (SH) after subdividing the later according to re-recurrence status. METHODS: Between 2001 and 2013, patients who received hepatectomy for CLM and R-CLM were included in study. Patients with non-resectable R-CLM were excluded. RESULTS: One hundred sixteen patients were included: 86 patients in SH group and 30 patients in RH group. Repeat hepatectomy group had more synchronous CLM (76.7 versus 50 %, p = 0.011). From the 86 patients who underwent SH, 69 patients did not have R-CLM. Survival analysis was done from the time of first hepatectomy for the no R-CLM group and the time of RH for the RH group. The 3- and 5-year survival rates for the no R-CLM group were 66.4 and 48.8%, respectively, and for the RH group were 56 and 44.8% respectively (p = 0.841). Multivariate analysis showed that larger size of R-CLM is an independent risk factor for survival after RH. CONCLUSION: Repeat hepatectomy for R-CLM shows a comparable OS to non-recurrent CLM after single hepatectomy, despite the RH group had higher incidence of synchronous CLM.

Survival after Liver Transplant: Influence of Progression of Disease and of Restoration of the "Milan" Criteria in Patients with Hepato-cellular Carcinoma undergoing Down-staging Procedures.

BACKGROUND/AIMS: Selection of patients with hepa- to-cellular carcinoma for liver transplantation is gen- erally performed according to the so-called Milan cri- teria. The aim of this study was to learn whether, after down-staging loco-regional therapies, patients origi- nally non-fulfilling the MC (Milan-OUT) meet these criteria (Milan-IN). METHODOLOGY: Between January 2000 and December 2008, 172 patients with HCC re- ceived LT at our Department. Of these, 142 were sub- jected to DS before LT. RESULTS: Of the 142 patients who received DS, 115 (81%) were Milan-IN and 27 (19%) were Milan-OUT at the time of their enrollment in the waiting list for LT. After a median follow-up of 50 months, overall 1-, 3-, and 5-year survival and dis- ease recurrence-free survival were not significantly different. CONCLUSIONS: Patients with Milan-OUT HCC can be successfully subjected to LT when they fulfill the MC after being subjected to DS. Imaging progres- sion while on the waiting list is a strong predictor of high rates of HCC recurrence even in patients meet- ing the MC. Lack of imaging progression seems to be a strong predictor of positive LT outcome and should be added to the eligibility criteria for the assessment of LT candidates with HCC.

Evolution of robotic nephrectomy for living donation: from hand-assisted to totally robotic technique.

BACKGROUND: The application of robotic-assisted surgery offers EndoWrist instruments and 3-D visualization of the operative field, which are improvements over traditional laparoscopy. The results of the few studies published so far have shown that living donor nephrectomy using the robot-assisted technique is safe, feasible, and offers advantages to patients. MATERIALS AND METHODS: Since November 2009, 16 patients have undergone robotic-assisted living donor nephrectomy at our Institute. Patients were divided into two groups according to the surgical technique adopted for the procedure: Group A, hand-assisted robotic nephrectomy (eight patients); Group B, totally robotic nephrectomy (eight patients). RESULTS: Intra-operative bleeding was similar in the two groups (90 vs 100 mL for Group A and B, respectively). Median warm ischemia time was significantly shorter in Group A (2.3 vs 5.1 min for Group A and B, respectively, P-value = 0.05). Switching to the open procedure was never required. Median operative time was not significantly longer in Group A than Group B (275 min vs 250 min, respectively). CONCLUSION: Robotic assisted living kidney recovery is a safe and effective procedure. Considering the overall technical, clinical, and feasibility aspects of living kidney donation, we believe that the robotic assisted technique is the method of choice for surgeon's comfort and donors' safety.

Liver transplantation for hepatocellular carcinoma recurrence after liver resection: why deny this chance of cure?

INTRODUCTION: Liver transplantation (LT) after liver resection (LR) for hepatocellular carcinoma (HCC) recurrence may be associated with poor patient long-term results and higher perioperative patient morbidity and mortality. This study focused on short-term and long-term outcomes of LT recipients due to HCC recurrence after LR in a single-institution cohort, and in highly comparable case-matched subgroups. METHODS: Between 2000 and 2009, 570 consecutive patients with documented HCC underwent LR (n=355, 62.2%) or LT (n=215, 37.8%) at our Institute. The case-matched analysis was between 2 groups: group A1, LT recipients who had already undergone LR (n=26); group B1, LT recipients who had not already undergone LR (n=26). RESULTS: Patient morbidity was higher in the A1 group in terms of packed red blood cell units transfused, fresh frozen plasma units transfused, median operative time, postoperative bleeding, and postoperative reoperations. No differences were detected in terms of patient mortality, patient survival, and patient recurrence-free survival at the univariate and multivariate analysis. CONCLUSIONS: Although LT among patients who have already undergone LR is associated with higher risk of patient morbidity, patient long-term survival and recurrence-free survival is not impaired. Therefore, there do not seem to be any valid reasons to deny the chance of LT to patients who have already undergone LR.

Laparoscopic versus open liver surgery: a single center analysis of post-operative in-hospital and post-discharge results.

PURPOSE: Laparoscopic hepatectomy (LH) is established as a safe and feasible surgical procedure for benign and malignant liver lesions showing many benefits in terms of short-term post-operative outcomes. Nevertheless, it remains unclear if these benefits extend beyond the hospital stay. The aim of this study was to compare in-hospital and post-discharge outcomes between two groups of patients who have undergone either laparoscopic or open hepatectomy (OH). METHODS: Forty-six patients who have undergone LH from September 2008 to September 2011 were compared to 46 matched-pair control patients who have undergone OH. The two groups were compared in terms of in-hospital and 6-month outcomes. Post-discharge outcomes were analyzed in terms of the number of outpatient clinic appointments (OCAs) and readmissions (RAs). Analyses were performed excluding and including conversion cases. RESULTS: The two groups resulted in homogeneous patients' and lesions' characteristics. Patients who underwent LH showed statistically lower intra-operative blood loss, less total and major morbidity and shorter hospital stay. Regarding post-discharge outcomes, significantly less patients of LH group compared to patients of OH group required more than two post-discharge OCAs (in the intention to treat analysis, 28.3 versus 63%, respectively; P = 0.006) or RA (4.3 versus 15.2%, respectively; P = 0.008). The benefits of LH appeared to be maximized in cirrhotic patients; those represented the large part of patients readmitted after hepatectomy regardless of the type of surgical approach (77.8%). CONCLUSIONS: Advantages related to LH extend over the post-discharge period suggesting potential better patient's satisfaction and lower hospital cost.

Living donor liver transplantation for hepatocellular carcinoma: the impact of neo-adjuvant treatments on the long term results.

BACKGROUND/AIMS: LDLT may represent a valid therapeutic option allowing several advantages for patients affected by HCC and waiting for liver transplantation (LT). However, some reports show a worse long term survival and disease free survival among patients treated by LDLT for HCC than deceased donor liver transplantation (DDLT) recipients. METHODOLOGY: Among 1145 LT patients, 63 received LDLT. From January 2000 to December 2008, 179 patients underwent LT due to HCC, 30 (16.7%) received LDLT and 154 (86.0%) received DDLT. Patients were selected based on the Milan criteria. TACE, radiofrequency ablation, percutaneous alcoholization, or liver resection were applied as downstaging procedures, while on the waiting list. RESULTS: Overall 3- and 5-year survival rate was 77.3% and 68.7% vs. 82.8% and 76.7%, respectively for LDLT and DDLT recipient with not significant differences. Moreover, 3- and 5- years of recurrence free survival rate was 95.5% (LDLT) vs. 90.5% and 89.4% (DDLT) and resulted not significantly different. CONCLUSIONS: LDLT guarantees same long term results than DDLT if the selection criteria of candidates are analogues. Milan criteria remains a valid candidate selection tool to obtain optimal long term results in LDLT. An aggressive downstaging policy seems to improve the long-term results in LDLT, thus LRT may be considered useful to prevent tumor progression waiting for transplantation as well as a neoadjuvant therapy for HCC. A literature detailed meta-analysis could definitely clarify if LDLT is an independent risk factor for HCC recurrence.

Beyond the Milan criteria: what risks for patients with hepatocellular carcinoma progression before liver transplantation?

BACKGROUND: To date the selection of the best candidates for liver transplantation (LT) owing to hepatocellular carcinoma (HCC) has been mainly based on tumor morphological characteristics (nodule diameter and number), which have resulted to be independent risk factors for short long-term survival and a high rate of tumor recurrence. METHODS: The study cohort included 118 patients among the 166 with HCC transplanted at our unit from January 2000 to December 2007. Patients were classified according to response to locoregional treatments before LT: progressive Group A; complete Group B; partial Group C; stable Group D. RESULTS: The 3-year and 5-year overall survival rates were 65.5% and 48.9% for Group A versus 84.8% and 74.6% for Group BCD (P = 0.01). The 3-year and 5-year disease-free survival rates were 74% and 74% for Group A and 95.7% and 93% for Group BCD (P = 0.007). HCC progression was the only independent risk factor according to Cox regression P = 0.014--odds ratio 4.4 (1.35-14.3). CONCLUSION: After aggressive HCC treatment before LT, imaging progression while on the waiting list was a strong predictor of high HCC recurrence rate also in patients who met the Milan criteria. Lack of imaging progression can contribute toward the selection of good transplant candidates for HCC together with the Milan criteria.

Percutaneous Transhepatic Bile Duct Ablation with n-Butyl Cyanoacrylate in the Treatment of a Biliary Complication after Split Liver Transplantation.

Biliary complications continue to be a major cause of morbidity after split-liver transplantation (SLT). In this report we describe an uncommon late biliary complication. One year after SLT the patient showed an intrahepatic bile dicy dilatation with severe cholangitis episodes. The segmentary bile duct of hepatic segment VI-VII draining in the left duct was unidentified and tied at the time of the in situ split-liver procedure. We perform a permanent obliteration of the dilated intrahepatic ducts by a percutaneous embolization using an n-butyl cyanoacrylate (NABC). The management of biliary complications after SLT requires a multidisciplinary approach. The use of NBCA in obliteration of a dilated bile duct seems to be a safe procedure with good results providing a less invasive option than hepatic resection and decreasing the morbidity associated with chronic external biliary drainage. Further studies are needed to determine whether this approach is effective and safe and whether it could reduce hospital stay and cost.

Should we still offer split-liver transplantation for two adult recipients? A retrospective study of our experience.

The role of split-liver transplantation (SLT) for two adult recipients is still a matter of debate, and no agreement exists on indications, surgical techniques, and results. The aim of this study was to retrospectively analyze the outcome of our series of SLT. From May 1999 to December 2006, 16 patients underwent SLT at our unit. We used 9 full right grafts (segments 5-8) and 7 full left grafts (segments 1-4). The splitting procedure was always carried out in situ with a fully perfused liver. Postoperative complications were recorded in 8 (50%) patients: 5 (55%) in full right grafts and 3 (43%) in full left grafts. No one was retransplanted. After a median follow-up of 55.82 months (range, 0.4-91.2), 5 (31%) patients died, and the 1-, 3-, and 5-year overall survival rate for patients and grafts was 69%. We considered as a control group for the global outcome 232 whole liver transplantations performed at our unit in the same period of time. Postoperative complications were recorded in 53 (23%) patients, and after a median follow-up of 57.37 months (mean, 55.11; range, 1-102.83), the 1-, 3-, and 5-year overall patient survival was 87%, 82%, and 80%, respectively. In conclusion, SLT for two adult recipients is a technically demanding procedure that requires complex logistics and surgical teams experienced in both liver resection and transplantation. Although the reported rate of survival might be adequate for such a procedure, more efforts have to be made to improve the short-term outcome, which is inadequate in our opinion. The true feasibility of SLT for two adults has to be considered as still under investigation.

Biliary complications after living donor adult liver transplantation.

The highest rate of complications characterizing the adult living donor liver transplantation (ALDLT) are due to biliary problems with a reported negative incidence of 22-64%. We performed 23 ALDLT grafting segments V-VIII without the middle hepatic vein from March 2001 to September 2005. Biliary anatomy was investigated using intraoperative cholangiography alone in the first five cases and magnetic resonance cholangiography in the remaining 18 cases. In 13 cases we found a single right biliary duct (56.5%) and in 10 we found multiple biliary ducts (43.7%). We performed single biliary anastomosis in 17 cases (73.91%) and double anastomosis in the remaining six (26%) cases. With a mean follow up of 644 days (8-1598 days), patient and graft survivals are 86.95% and 78.26%, respectively. The following biliary complications were observed: biliary leak from the cutting surface: three, anastomotic leak: two, late anastomotic strictures: five, early kinking of the choledochus: one. These 11 biliary complications (47.82%) occurred in eight patients (34.78%). Three of these patients developed two consecutive and different biliary complications. Biliary complications affected our series of ALDLT with a high percentage, but none of the grafts transplanted was lost because of biliary problems. Multiple biliary reconstructions are strongly related with a high risk of complication.