How useful is the machine perfusion in liver transplantation? An answer from a national survey.

Machine perfusion (MP) has been shown worldwide to offer many advantages in liver transplantation, but it still has some gray areas. The purpose of the study is to evaluate the donor risk factors of grafts, perfused with any MP, that might predict an ineffective MP setting and those would trigger post-transplant early allograft dysfunction (EAD). Data from donors of all MP-perfused grafts at six liver transplant centers have been analyzed, whether implanted or discarded after perfusion. The first endpoint was the negative events after perfusion (NegE), which is the number of grafts discarded plus those that were implanted but lost after the transplant. A risk factor analysis for NegE was performed and marginal grafts for MP were identified. Finally, the risk of EAD was analyzed, considering only implanted grafts. From 2015 to September 2019, 158 grafts were perfused with MP: 151 grafts were implanted and 7 were discarded after the MP phase because they did not reach viability criteria. Of 151, 15 grafts were lost after transplant, so the NegE group consisted of 22 donors. In univariate analysis, the donor risk index >1.7, the presence of hypertension in the medical history, static cold ischemia time, and the moderate or severe macrovesicular steatosis were the significant factors for NegE. Multivariate analysis confirmed that macrosteatosis >30% was an independent risk factor for NegE (odd ratio 5.643, p = 0.023, 95% confidence interval, 1.27-24.98). Of 151 transplanted patients, 34% experienced EAD and had worse 1- and 3-year-survival, compared with those who did not face EAD (NoEAD), 96% and 96% for EAD vs. 89% and 71% for NoEAD, respectively (p = 0.03). None of the donor/graft characteristics was associated with EAD even if the graft was moderately steatotic or fibrotic or from an aged donor. For the first time, this study shows that macrovesicular steatosis >30% might be a warning factor involved in the risk of graft loss or a cause of graft discard after the MP treatment. On the other hand, the MP seems to be useful in reducing the donor and graft weight in the development of EAD.

Major hepatectomy for perihilar cholangiocarcinoma in elderly patients: is it reasonable?

INTRODUCTION: We sought to evaluate the effect of age on postoperative outcomes among patients undergoing major liver surgery for perihilar cholangiocarcinoma (PHCC). METHODS: 77 patients were included. Patients were categorized into two groups: the "< 70-year-olds" group (n = 54) and the "≥ 70-year-olds" group (n = 23). RESULTS: Median LOS was 19 both for < 70-year-old group and ≥ 70-year-old group (P = 0.72). No differences in terms of severe complication were detected (44.4% Clavien-Dindo 3-4-5 in < 70-year-old group vs 47.8% in ≥ 70-year-old group, P = 0.60). Within 90 postoperative days, 11 patients died, 6 in < 70-year-old group (11.3%) and 5 in ≥ 70-year-old group (21.7%), P = 0.29. The median follow-up was 20 months. The death rate was 72.2% and 78.3% among patients < 70 years old and ≥ 70 years old. The OS at 2 and 5 years was significantly higher among the < 70 years old (57.0% and 27.7%) compared to the ≥ 70 years old (27.1% and 13.6%), P = 0.043. Adjusting for hypertension and Charlson comorbidity index in a multivariate analysis, the HR for age was 1.93 (95% CI 0.84-4.44), P = 0.12. Relapse occurred in 43 (81.1%) patients in the < 70-year-old group and in 19 (82.6%) patients in the ≥ 70-year-old group. DFS at 12, 24, and 36 months was, respectively, 59.6, 34.2, and 23.2 for the < 70 -year-old group and 32.5, 20.3, and 13.5 for the ≥ 70-year-old group (P = 0.26). Adjusting for hypertension and Charlson comorbidity index in a Cox model, the HR for age was 1.52 (95% CI 0.67-3.46), with P = 0.32. CONCLUSIONS: ≥ 70-year-old patients with PHCC can still be eligible for major liver resection with acceptable complication rates and should not be precluded a priori from a radical treatment.

Multicentre evaluation of case volume in minimally invasive hepatectomy.

BACKGROUND: Surgical outcomes may be associated with hospital volume and the influence of volume on minimally invasive liver surgery (MILS) is not known. METHODS: Patients entered into the prospective registry of the Italian Group of MILS from 2014 to 2018 were considered. Only centres with an accrual period of at least 12 months and stable MILS activity during the enrolment period were included. Case volume was defined by the mean number of minimally invasive liver resections performed per month (MILS/month). RESULTS: A total of 2225 MILS operations were undertaken by 46 centres; nine centres performed more than two MILS/month (1376 patients) and 37 centres carried out two or fewer MILS/month (849 patients). The proportion of resections of anterolateral segments decreased with case volume, whereas that of major hepatectomies increased. Left lateral sectionectomies and resections of anterolateral segments had similar outcome in the two groups. Resections of posterosuperior segments and major hepatectomies had higher overall and severe morbidity rates in centres performing two or fewer MILS/month than in those undertaking a larger number (posterosuperior segments resections: overall morbidity 30·4 versus 18·7 per cent respectively, and severe morbidity 9·9 versus 4·0 per cent; left hepatectomy: 46 versus 22 per cent, and 19 versus 5 per cent; right hepatectomy: 42 versus 34 per cent, and 25 versus 15 per cent). CONCLUSION: A volume-outcome association existed for minimally invasive hepatectomy. Complex and major resections may be best managed in high-volume centres.

ANTECEDENTES: Los resultados quirúrgicos pueden estar relacionados con el volumen de casos del hospital, pero no se conoce la influencia en la cirugía mínimamente invasiva del hígado (minimally­invasive liver surgery, MILS). MÉTODOS: Se incluyeron los pacientes registrados en el registro prospectivo del grupo italiano de MILS desde 2014 a 2018. Solo se consideraron centros con extensión de ≥ 12 meses y actividad estable de MILS durante el periodo de reclutamiento. El volumen de casos se definió como el número de MILS efectuado por mes. RESULTADOS: Se llevaron a cabo un total de 2.225 MILS en 46 centros, 9 de ellos con > 2 MILS/mes (n = 1.376 pacientes) y 37 centros con ≤ 2 MILS/mes (n = 849). La proporción de resecciones de segmentos anterolaterales disminuyó con el volumen de casos, mientras que la proporción de hepatectomías mayores aumentó. Los resultados para ambos grupos fueron similares en las seccionectomías lateral izquierda y en las resecciones del segmento anterolateral. Las resecciones del segmento posterosuperior y las hepatectomías mayores presentaron tasas más altas de morbilidad global y morbilidad grave en centros que realizaban ≤ 2 MILS/mes que en los que realizaban > 2 MILS/mes (resecciones del segmento posterosuperior, morbilidad global 30,4 versus 18,7%, morbilidad grave 9,9 versus 4,0%; hepatectomía izquierda, 46,2 versus 22,0%, 19,2 versus 5,5%; hepatectomía derecha, 41,7 versus 33,8%, 25,0 versus 14.9%). CONCLUSIÓN: Se observó una asociación volumen­resultado para la resección hepática mínimamente invasiva. Las resecciones complejas y mayores se pueden manejar mejor en centros de gran volumen.

Risk-adjusted benchmarks in laparoscopic liver surgery in a national cohort.

BACKGROUND: This study aimed to assess the best achievable outcomes in laparoscopic liver resection (LLR) after risk adjustment based on surgical technical difficulty using a national registry. METHODS: LLRs registered in the Italian Group of Minimally Invasive Liver Surgery registry from November 2014 to March 2018 were considered. Benchmarks were calculated according to the Achievable Benchmark of Care (ABC™). LLRs at each centre were divided into three clusters (groups I, II and III) based on the Kawaguchi classification. ABCs for overall and major morbidity were calculated in each cluster. Multivariable analysis was used to identify independent risk factors for overall and major morbidity. Significant variables were used in further risk adjustment. RESULTS: A total of 1752 of 2263 patients fulfilled the inclusion criteria: 1096 (62·6 per cent) in group I, 435 (24·8 per cent) in group II and 221 (12·6 per cent) in group III. The ABCs for overall morbidity (7·8, 14·2 and 26·4 per cent for grades I, II and II respectively) and major morbidity (1·4, 2·2 and 5·7 per cent) increased with the difficulty of LLR. Multivariable analysis showed an increased risk of overall morbidity associated with multiple LLRs (odds ratio (OR) 1·35), simultaneous intestinal resection (OR 3·76) and cirrhosis (OR 1·83), and an increased risk of major morbidity with intestinal resection (OR 4·61). ABCs for overall and major morbidity were 14·4 and 3·2 per cent respectively for multiple LLRs, 30 and 11·1 per cent for intestinal resection, and 14·9 and 4·8 per cent for cirrhosis. CONCLUSION: Overall morbidity benchmarks for LLR ranged from 7·8 to 26·4 per cent, and those for major morbidity from 1·4 to 5·7 per cent, depending on complexity. Benchmark values should be adjusted according to multiple LLRs or simultaneous intestinal resection and cirrhosis.

ANTECEDENTES: Este estudio tuvo como objetivo evaluar los mejores resultados que se pueden conseguir en la resección hepática laparoscópica (laparoscopic liver resection, LLR) después del ajuste por riesgos basado en la dificultad de la técnica quirúrgica utilizando un registro nacional. MÉTODOS: Se consideraron las LLRs incluidas en el Registro del Grupo Italiano de Cirugía Hepática Mínimamente Invasiva desde 11/2014 a 03/2018. Los resultados de referencia (benchmarks) se calcularon de acuerdo con el Achievable Benchmark of Care (ABC™). Las LLRs de cada uno de los centros se dividieron en 3 grupos (Grupo I, II y III) en base a la clasificación de Kawaguchi. Se calculó el ABC de la morbilidad global y de la morbilidad mayor para cada grupo. Se realizó un análisis multivariable para identificar los factores independientes de riesgos para la morbilidad global y morbilidad mayor. Se utilizaron variables significativas para realizar ajustes de riesgo adicionales. RESULTADOS: Un total de 1.752 pacientes de los 2.263 cumplían los criterios de inclusión, de los cuales 1.096 (62,6%) se incluyeron en el Grupo I, 435 (24,8%) en el Grupo II y 221 (12,6%) en el Grupo III. El ABC de la morbilidad global (7,8%, 14,2%, 26,4%) y de la morbilidad mayor (1,4%, 2,2%, 5,7%) aumentó del Grupo I al Grupo III. El análisis multivariable mostró un incremento del riesgo para la morbilidad global asociada con múltiples LLRs (razón de oportunidades, odds ratio, OR 1,349), resección intestinal simultánea (OR 3,760) y cirrosis (OR 1,825), y para la morbilidad mayor con la resección intestinal (OR 4,606). Los ABC de la morbilidad global y morbilidad mayor fueron 14,4% y 3,2% para las LLR múltiples, 30% y 11% para la resección intestinal, y 14,9% y 4,8% para la cirrosis, respectivamente. CONCLUSIÓN: Los resultados de referencia (benchmark) para la morbilidad global y morbilidad mayor en la LLR variaron entre un 8% y un 26% y entre un 1,4% y un 5,7%, dependiendo de la complejidad. Los valores de referencia deberían ajustarse de acuerdo con la práctica de LLRs múltiples o resección intestinal simultánea y cirrosis.

Single Hepatocellular Carcinoma approached by curative-intent treatment: A propensity score analysis comparing radiofrequency ablation and liver resection.

INTRODUCTION: Patients with a single small Hepatocellular Carcinoma (HCC) may be definitively treated by Radiofrequency ablation (RFA) with a very low rate of peri-operative morbidity. However, results are still controversial comparing RFA to Liver Resection (LR). METHODS: All consecutive patients treated by RFA or LR for a single untreated small HCC on liver cirrhosis between January 2006-December 2016 were enrolled. Patients were matched 1:1 basing on: age, MELD-score, platelet count, nodule's diameter, HCV status, α-fetoprotein level, and Albumin-Bilirubin score. First analysis compered LR to RFA. Second analysis compared Laparoscopic LR (LLR) to RFA. RESULTS: Of 484 patients with single small HCC, 91 patients were selected for each group after a 1:1 propensity score matching (PS-M). The 5-years OS was 70% and 60% respectively for LR and RFA group (P = 0.666). The 5-year RFS was 36% and 21% respectively for LR and RFA group (P < 0.001). Patients treated by LR had a significantly longer hospital stay and higher complications rate. Comparing 50 cases of LLR and 50 of RFA, the 5-years OS was 79% and 56% respectively for LLR and RFA group (P = 0.22). The 5-year RFS was 54% and 19% respectively for LR and RFA group (P < 0.001). Post-operative complications were not significantly different. CONCLUSIONS: LLR confers similar peri-operative complications rate compared to RFA. LLR should be considered as a first-line approach for the treatment of a single small HCC as it combines the effectiveness of open LR and the safety profile of RFA.

Intramuscular islet allotransplantation in type 1 diabetes mellitus.

OBJECTIVE: Alternative sites to the liver for islet transplantation have been studied for a long time. Intramuscular islet transplantation appears to be an alternative site to the liver because of the ease of access. First islet autotransplantations were reported in patients after total pancreatectomies. The transplanted islets showed a proper revascularization and their function was observed for up to 2 years after the implant. However, only a few cases of autotransplantation and no allotransplantation have been performed. The aim of this study was to verify the feasibility of islet allotransplantation into muscles. PATIENTS AND METHODS: In four patients affected by type 1 diabetes mellitus in which liver islet allotransplantation was contraindicated, human islets were transplanted into patients' arm muscle with local anesthesia. RESULTS: The surgery was minimally invasive, without complications. In one patient a moderate local inflammatory reaction was observed at the site of the implant, which resolved spontaneously within 4 days. Islet graft function was observed after transplantation in all patients, but it progressively disappeared in 3 out 4 patients within a short time. CONCLUSIONS: In this first ever-reported intramuscular pancreatic islet allotransplantation, the procedure appears feasible but new strategies must be envisaged to significantly improve islet engraftment and the long-term graft function.

Robot-Assisted Harvesting of Kidneys for Transplantation and Global Complications for the Donor.

INTRODUCTION: Robot-assisted kidney harvesting from living donors is feasible and safe. We report the results of a mono-centric experience relative to 98 consecutive robotic nephrectomies with emphasis on global donor complications. MATERIALS AND METHODS: This is a retrospective cohort study. Donors underwent robot-assisted kidney harvesting. The preferred kidney was the left one even in the presence of vascular anomalies. In the first cases we used a robotic hand-assisted technique, then the totally robotic technique, and finally the modified totally robot-assisted technique. Postoperative complications were ranked according to the five-grade Clavien-Dindo classification. RESULTS: Between November 2009 and November 2016, 98 living donors underwent nephrectomy. We experienced 14 complications. The 3 intraoperative ones (3.06%) were 1 pneumothorax and 2 acute bleedings, 1 of them requiring transfusion. The 11 postoperative complications (11.22%) were as follows: 5 wound seromas, 1 rhabdomyolisis (Clavien I), 1 paretic ileum, 1 anemia requiring transfusion, 1 hypertensive crisis (Clavien II), and 2 chylus collections drained by interventional radiologists (Clavien III). Transfusion rate was 2.1%; conversions, reoperations, and mortality were nil. No statistically significant difference was observed between the patients with complications and without in terms of gender, age, anatomical anomalies, body mass index (BMI), and learning curve. We observed a longer global operation length of time in patients with complications. CONCLUSION: Robotic assistance results in shorter and simpler learning curves for the harvesting of kidneys from living donors. It enables an easier and more efficient management of possible intraoperative complications. The rate of postoperative complications is comparable with the rate of complications encountered in traditional laparoscopic series with high numbers of harvestings.

Dual Kidney Transplantation: Evaluation of Recipient Selection Criteria at Niguarda Hospital.

BACKGROUND: Dual kidney transplantation (DKT) is a largely accepted strategy to enlarge the donor pool. Niguarda Hospital started this program in December 2010, and 38 DKT have been performed. In our series, we included recipients older than those in the other series published in literature. The aim of this study was to know if our recipient selection criteria for DKT are safe. METHODS: We reviewed our data base of DKT and analyzed recipients' medical history, surgical technique, post-operative complications, graft survival, morbidity, and mortality. We then compared our results with the literature. RESULTS: From December 2010 to April 2015, 38 DKT were performed in Niguarda Hospital. Delayed graft function was present in 21 recipients. Explantation of both kidneys was performed in 1 patient and explantation of 1 kidney in 6 patients. Post-operative complications were present in 8 patients. Five patients returned to hemodialysis after DKT. One recipient died of medical post-operative sepsis. The mean follow-up was 24 months. Graft survival and patient survival were 86.84% and 97.93%, respectively. Compared with the literature, our series had similar mortality and morbidity rates, even if recipients' age was higher than in other series. CONCLUSIONS: The strategy of DKT allocation in elderly recipients is safe. Further studies have to be performed to optimized selection of the recipients for DKT not to disadvantage younger patients in the transplant waiting list and to improve the technique of organ evaluation and preservation to refine graft allocation.

Do Older Liver Grafts Have Worse Survival? The Niguarda Experience.

BACKGROUND: Elderly donor livers are thought to be marginal graft. In the present study, we aimed to identify an age threshold to consider a graft as elderly to identify the trend (if any) of the donor age in our series and to identify an efficient allocation criteria for elderly grafts. METHODS: We reviewed in a retrospective manner our series of 1520 liver transplants, comparing graft survival under and over a certain age. On the basis of the results of this analysis, we identified a threshold of 70 years to define a graft as old. The donor age trend analysis showed an increasing rate of transplants from elderly donors. RESULTS: To identify efficient allocation criteria for elderly graft, we stratified the series by the disease of the recipient: 556 patients underwent transplants for hepatocellular carcinoma (HCC+ group) and 964 for other diseases (HCC- group). Two hundred twenty-one patients of 556 of the HCC+ group were hepatitis c virus (HCV) negative (HCC+/HCV- group), and 312 of 964 of the HCC- group were HCV positive (HCC-/HCV+). The survival analysis showed no significant differences in comparing the outcome for elderly and young grafts in the HCC+ (P = .135) and HCC- (P = .055) groups. CONCLUSIONS: When comparing the survival of old and young livers in the HCC+/HCV- group, the elderly livers appear to have a better outcome (P = .05); on the other hand, the same analysis in the HCC-/HCV+ group shows a worse outcome for old-aged grafts (P = .026). Therefore, the present study suggests that elderly livers should be allocated to hepatocellular carcinoma (HCC) patients and should be avoided in HCV+ recipients.

Split-liver full-left full-right: proposal for an operative protocol.

INTRODUCTION: Worldwide, organ shortage is a major limiting factor to transplantations. One possible way to face graft scarcity is splitting full livers into hemilivers; this procedure would allow transplantation in 2 adult recipients with the use of a single organ from a deceased donor. OBJECTIVE: The goal of this study was to describe an adult-to-adult split liver operative protocol and share it between centers interested in exploring this procedure. MATERIALS AND METHODS: A literature review was first conducted to elaborate on the present protocol; second, selection criteria for suitable deceased donors were identified. The technical aspects of performing the procurement were also analyzed; finally, the recipient selection criteria and the transplantation criteria were determined. RESULTS: The donor characteristics should be consistent with the following: age≤55 years; weight≥70 kg; body mass index<28 kg/m2; intensive care unit stay<7 days; sodium level<160 mEq/L if the intensive care unit stay is >2 days; maximum transaminase value 3 times normal; hemodynamic stability; negative for hepatitis B surface antigen, hepatitis C virus, and human immunodeficiency virus; macrosteatosis<20%; macroscopic adequacy; and absence of anatomic anomalies requiring complex reconstruction. The procurement hospital should provide the preoperative computed tomography scan, liver dissector, and the intraoperative ultrasound. Indication for in situ or ex situ splitting depends on the hepatic vein outflow anatomy. Graft-to-recipient weight ratio should be ≥1%, and the graft-to-recipient spleen size ratio should be ≥0.6. United Network for Organ Sharing status 1 and 2A recipients are excluded, as are patients with transjugular intrahepatic portosystemic shunts. Hemiliver transplants are performed as in living-donor liver transplantation, and portal hyperflow is corrected by splenic artery ligation, splenectomy, and portal infusion of vasoactive drugs. CONCLUSIONS: The present protocol was proposed to test the validity of the full-left full-right split liver procedure. A retrospective analysis found that 130 transplantations were suitable for this procedure according to the present protocol in the period January 1, 2008, through December 31, 2011 (65 donors). We believe that these numbers could be greatly increased once this procedure is proven feasible and safe within the proposed criteria.

Initial experience with robot-assisted nephrectomy for living-donor kidney transplantation: feasibility and technical notes.

BACKGROUND: Robot-assisted surgery provide endowrist instruments and 3-dimensional visualization of the operative field that are improvements over traditional laparoscopy. The few research studies published so far have demonstrated that living-donor nephrectomy using the robot-assisted technique is safe and feasible, providing advantages for patients. METHODS: Since November 2009, we performed 20 robot-assisted living-donor nephrectomies. Eight patients underwent hand-assisted robotic nephrectomy, whereas 20, totally robotic nephrectomy. RESULTS: Median intraoperative bleeding was 174 mL (range, 10-750) but no patient needed intraoperative transfusion with blood cells. The median warm ischemia time was 3.16 minutes (range, 0.30-6.5). there was no case of conversion to an open procedure. The median operative time was 311 minutes (range, 85-530); the median console time was 160 minutes (range, 135-220). CONCLUSION: Robot-assisted living-donor kidney recovery was a safe and effective procedure. The totally robotic recovery is an evolving technique. The prospect of robotic staplers, endowrist ligature, and robotic single port may further increase these advantages.

Living-donor liver transplantation: donor selection criteria and postoperative outcomes. A single-center experience with a 10-year follow-up.

BACKGROUND: Donor safety must be considered to be a priority in live-donor liver transplantation (LDLT). The aim of this study was to evaluate these outcomes with special attention to surgical complications and their treatment. METHODS: From March 2001 to March 2012, 80 live donors underwent right hepatectomy (5-8 segments). The middle hepatic vein was always left in the donor. Our retrospective study analyzed surgical outcomes and complications according to the Clavien classification modified for live donors. RESULTS: With a median follow up of 63.2 ± 12.6 months, the mortality was 0%. Two donors experienced intraoperative complications, but all of them had complete recovery there after. Among the 22 complications in 17 donors (21.2%), 7 (8.7%) were major complications (Clavien grade 2b) but only 2 donors required surgical treatment. CONCLUSIONS: LDLT is a safe and feasible modality to alleviate the cadaveric donor shortage. The efficacy of this procedure is similar to that with deceased donors.

Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study.

In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m(2) (97.5% CI 1.9, 11.4 mL/min/1.73 m(2), p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m(2) in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m(2) in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant.

Colorectal liver metastases: hepatic pedicle clamping during hepatectomy reduces the incidence of tumor recurrence in selected patients. Case-matched analysis.

BACKGROUND: Hepatic pedicle clamping (HPC) during Liver Resection (LR) is a vascular procedure designed to prevent bleeding from the liver during hepatectomy. Outgrowth of pre-existing colorectal micrometastases may occur 5-6 times faster in occluded liver lobes than in non-occluded lobes. We conducted a case-matched analysis at our Institution to assess the effects of HPC on overall and recurrence-free survival in highly selected patients, who underwent LR due to Colorectal liver metastases (CLM). MATERIALS AND METHODS: From January 2002 to December 2010, 120 patients operated for CLM were included into this case-matched study. Patients were allocated to two groups: Group-A patients who underwent HPC during LR; Group-B patients who underwent LR without HPC. RESULTS: HPC during liver resection was associated with better overall patient 5-year survival (47.2% in Group-A and 32.1% in Group-B) (P-value = 0.06), and significantly better 5-year recurrence-free survival (49.9% in Group-A vs 18.3% in Group-B) (P-value = 0.010) The Cox regression model identified the following risk factors for worse prognosis in terms of shorter recurrence-free survival and higher incidence of tumor recurrence: no HPC (Group-B) (P-value = 0.032) and positive lymph nodes at the time of LR (P-value = 0.018). CONCLUSION: Lack of HPC in selected patients who underwent LR for CLM results to be a strong independent risk factor for higher patient exposure to tumor recurrence. We suggest that hepatic hilum clamping should be seriously taken into consideration in this patient setting. MINI-ABSTRACT: A case-matched study was performed in 120 patients undergoing liver resection due to colorectal liver metastases, comparing patients who received intermittent hepatic pedicle clamping (HPC) with those who did not. The 5-year overall survival rate was similar, but the 5-year recurrence-free rate was significantly higher with no HPC (p = 0.012).

Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a randomized controlled trial.

In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (-3.0%; 95% CI -8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m(2) , 97.5% CI 3.74, 13.27 mL/min/1.73 m(2) , p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation.

Full-right-full-left split liver transplantation: the retrospective analysis of an early multicenter experience including graft sharing.

Full-right-full-left split liver transplantation divides a donor liver into two grafts to be transplanted in adult-size patients. Major technical and organizational difficulties have limited its application to few single center series. We retrospectively analyzed the long-term results of the first multicenter series of this procedure with graft sharing. Between November 1998 and January 2005, 43 transplants were performed by five centers from 23 full-right-full-left in situ split liver procedures; 65% of the grafts were shared. A total of 31 (72%) patients had complications above grade II; 3 (6.9%) were retransplanted. Hospital mortality was 23% with sepsis as the main cause. Six patients died in the long term, two of them for a road accident. A total of 27 patients are alive after a median follow-up of 3200 days (2035-4256). Actuarial survival at 1 and 10 years were 72.1%, 62.6% and 65.1%, 57.9%, respectively for patients and grafts. These figures are similar to those reported for adult living donor liver transplantation by the European Registry over a similar period. Multicenter collaboration in sharing of these grafts is feasible and can help facing the organizational limits, thus increasing diffusion of full-right-full-left split liver transplantation.

The first report of orthotopic liver transplantation in the Western world.

Until the present time, the first experimental liver transplant which led to the development of human liver transplantation is attributed to C. Stuart Welch who performed a heterotopic transplant in the canine species in 1955. In 1956, Jack Cannon is credited with the first animal orthotopic liver transplant although the species was not disclosed. This report is intended to set the historical record straight by acknowledging that Vittorio Staudacher in 1952 was the first to perform a liver transplant in a large animal model.

Balancing donor and recipient risk factors in liver transplantation: the value of D-MELD with particular reference to HCV recipients.

Donor-recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3-year patient survival. D-MELD cutoff predictive of 5-year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44-2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24-0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11-1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51-0.93), retransplant (OR = 1.82; 95% CI, 1.16-2.87) and low-volume center (OR = 1.48; 95% CI, 1.11-1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59-2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29-0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.

Hepatocellular carcinoma in unrelated viral cirrhosis: long-term results after liver transplantation.

INTRODUCTION: Chronic viral hepatitis is considered to be the most significant risk factor for development of hepatocellular carcinoma (HCC). Nevertheless, about 5%-15% of HCC occur in noncirrhotic or virus-unrelated cirrhotic patients. The natural history of HCC in terms of incidence, clinical features, and tumor progression differs according to the underlying cancerogenic factors and differences in hepatocarcinogenetic pathways. Little is know about the relationship between HCC outcomes after liver transplantation (OLT) and the primary liver disease. We retrospectively analyzed the outcomes of patients transplanted due to HCC in settings of either virus-related or virus-unrelated cirrhosis. PATIENTS AND METHODS: From January 2000 to December 2007, 179 patients underwent OLT due to HCC: 157 (87.8%) affected by virus-related (group A) and 22 (12.2%) virus-unrelated cirrhosis (group B). We analyzed patient characteristics including demographics, tumor features, downstaging treatments, and recurrences. RESULTS: At a mean follow-up of 41.2 months, the 3- and 5-year overall long-term survivals between group A versus group B were 81% versus 75% and 85% versus 78.4% respectively (P = NS). The 3- and 5-year disease-free survivals between group A versus group B were 90.8% versus 89.6% and 85.6% versus 85.6%, respectively (P = NS). After OLT, HCC recurrences occurred in 14 group A (14/157, 8.9%) and 4 patients (4/22, 18.1%) group B subjects. DISCUSSION: Our data demonstrated that after OLT, HCC outcomes were not different between patients with virus-related or -unrelated cirrhosis. The direct oncogenetic role played by hepatitis B and C appear to not be associated with a greater risk to develop HCC recurrence.

Living donor liver transplantation for hepatocellular carcinoma: long-term results compared with deceased donor liver transplantation.

OBJECTIVE: Living donor liver transplantation (LDLT) may represent a valid therapeutic option allowing several advantages for patients affected by hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). However, some reports in the literature have demonstrated worse long-term and disease-free survivals among patients treated by LDLT than deceased donor liver transplantation (DDLT) for HCC. Herein we have reported our long-term results comparing LDLT with DDLT for HCC. PATIENTS AND METHODS: Among 179 patients who underwent OLT from January 2000 to December 2007, 25 (13.9%) received LDLT with HCC 154 (86.1%) received DDLT. Patients were selected based on the Milan criteria. Transarterial chemoembolization, radiofrequency ablation, percutaneous alcoholization, or liver resection was applied as a downstaging procedure while on the waiting list. Patients with stage II HCC were proposed for LDLT. RESULTS: The overall 3- and 5-year survival rates were 77.3% and 68.7% versus 82.8% and 76.7% for LDLT and DDLT recipients, respectively, with no significant difference by the log-rank test. Moreover, the 3- and 5-year recurrence-free survival rates were 95.5% and 95.5% (LDLT) versus 90.5% and 89.4% (DDLT; P = NS). CONCLUSIONS: LDLT guarantees the same long-term results as DDLT where there are analogous selection criteria for candidates. The Milan criteria remain a valid tool to select candidates for LDLT to achieve optimal long-term results.