Eva Montalvá

Expanded criteria for liver transplantation in patients with cirrhosis and hepatocellular carcinoma

Orthotopic liver transplantation (OLT) selection for patients with hepatocellular carcinoma (HCC) is a matter of debate. The Milan criteria (MC) have been largely adopted by the international community. The main aim of this study was to evaluate the survival rates and recurrence probabilities of a new proposal for criteria (up to 3 tumors, each no larger than 5 cm, and a cumulative tumor burden ≤ 10 cm). Patients with cirrhosis and HCC included on the waiting list (WL) from 1991 to 2006 were retrospectively analyzed. Outcomes in patients who had tumors within and beyond the MC were compared. The survival analysis was done (1) with the intention‐to‐treat principle and (2) among transplanted patients. A total of 281 patients were included in WL. Twenty‐four cases did not undergo OLT (a dropout rate of 8.5%); all but 1 case had tumors within the MC. Of the 257 transplanted patients, 26 had tumors beyond the MC in the pre‐OLT evaluation. Based on the intention‐to‐treat analysis, the 5‐year survival was 56% versus 66% in patients who had tumors within and beyond the MC, respectively (P = 0.487). Among transplanted patients, the 5‐year survival was 62% versus 69%, respectively (P = 0.734). Through multivariate analysis, microvascular invasion was an independent prognostic factor of poor survival (P = 0.004). The recurrence probabilities at 1 and 5 years were 7% versus 12% and 14% versus 28% in patients with tumors within and beyond the MC, respectively (P = 0.063). The multivariate analysis demonstrated that both poorly differentiated tumors (P < 0.001) and microvascular invasion (P < 0.001) increased the risk of recurrence. The expansion to up to 3 nodules, each up to 5 cm, and a cumulative tumor burden ≤ 10 cm did not result in a reduction of survival in comparison with patients who had tumors within the MC. Liver Transpl 14:1449–1460, 2008.

Lessons learned from anatomic variants of the hepatic artery in 1,081 transplanted livers

The aim of this study is to contribute our experience to the knowledge of the anatomic variations of the hepatic arterial supply. The surgical anatomy of the extrahepatic arterial vascularization was investigated prospectively in 1,081 donor cadaveric livers, transplanted at La Fe University Hospital from January 1991 to August 2004. The vascular anatomy of the hepatic grafts was classified according to Michels description (Am J Surg 1966;112:337‐347) plus 2 variations. Anatomical variants of the classical pattern were detected in 30% of the livers (n = 320). The most common variant was a replaced left artery arising from the left gastric artery (9.7%) followed by a replaced right hepatic artery arising from the superior mesenteric artery (7.8%). In conclusion, the information about the different hepatic arterial patterns can help in reducing the risks of iatrogenic complications, which in turn may result in better outcomes not only following surgical interventions but also in the context of radiological treatments. Liver Transpl 13:1401–1404, 2007.

Effect of Calcineurin Inhibitors in the Outcome of Liver Transplantation in Hepatitis C Virus-Positive Recipients

Background. There is a paucity of good studies evaluating the impact of calcineurin inhibitors on posttransplantation outcome in hepatitis C virus (HCV)-infected liver transplant (LT) recipients. Methods. We sought to determine whether there are differences on posttransplantation survival and histologic recurrence in HCV-LT recipients based on initial immunosuppression (IS) by conducting a prospective study comparing tacrolimus (Tac) versus cyclosporine-based IS in patients undergoing LT between 2001 and 2007. Protocol liver biopsies were performed. Results. Baseline characteristics (demographics, liver function at LT, genotype distribution, donor, surgery, and IS except for the type of calcineurin inhibitor) did not differ between groups. Severe disease (defined as bridging fibrosis, cirrhosis, cholestatic hepatitis, or allograft loss or death because of recurrent disease in the first year) was present in 67 of 253 (26.5%) and was equally distributed in the CsA and Tac groups (27% vs. 26%; P=0.68). Two thirds of protocol biopsies performed at 1 year showed some fibrosis without differences between CsA and Tac groups (75% vs. 70%). Advanced fibrosis (bridging fibrosis and cirrhosis) was diagnosed in 30% CsA and 24.5% Tac patients (P=NS). No differences in survival at 1 and 7 years were observed (83% and 67% vs. 78% and 64%, respectively, P=0.4). In summary, in patients undergoing LT for HCV-related liver disease, posttransplantation outcome is not related to the calcineurin inhibitor used.

Comparative prospective study of two liver graft preservation solutions: University of Wisconsin and Celsior

University of Wisconsin solution (UWS) is the gold standard for graft preservation. Celsior solution (CS) is a new solution not as yet widely used in liver grafts. The aim of this study was to compare the liver function of transplanted grafts stored in these 2 preservation solutions. The primary endpoints were the rates of primary nonfunction (PNF) and primary dysfunction (PDF). We performed a prospective and pseudorandomized study that included 196 patients (representing 104 and 92 livers preserved in UWS and CS, respectively) at La Fe University Hospital (Valencia, Spain) between March 2003 and May 2005. PNF and PDF rates, liver function laboratory parameters, postoperative bleeding, vascular and biliary complications, and patient and graft survival at 3 years were compared for the 2 groups. The 2 groups were similar in terms of donor variables, recipient variables, and surgical techniques. The PNF rates were 2.2% and 1.9% in the CS and UWS groups, respectively (P = not significant), and the PDF rates were 15.2% and 15.5% in the CS and UWS groups, respectively (P = not significant). There were no significant differences in the laboratory parameters for the 2 groups, except for alanine aminotransferase levels in month 3, which were lower in the CS group (P = 0.01). No significant differences were observed in terms of complications. Three‐year patient and graft survival rates were as follows for years 1, 2, and 3: 83%, 80%, and 76% (patient) and 80%, 77%, and 73% (graft) for the UWS group and 83%, 77%, and 70% (patient) and 81%, 73%, and 67% (graft) for the CS group (P = not significant). In conclusion, this study shows that CS is as effective as UWS in liver preservation. Liver Transpl 15:1709–1717, 2009.

Long‐term outcome of ‘long‐term liver transplant survivors’

There are few studies focusing on long‐term complications in liver transplant (LT) recipients. The aim of this study was to define the outcome of LT recipients having survived at least 10 years from LT. Of 323 adult LT done between 1991 and 1997, the 167(52%) alive >10 years post‐LT (baseline time) formed the study population. Long‐term outcome measures included the following: immunosuppression, metabolic complications [obesity, arterial hypertension (AH), diabetes, dislypidemia], cardiovascular events (CVE), chronic renal dysfunction‐CRD, and de novo tumors. Median age at LT was 50 years. Most common indication was postnecrotic cirrhosis (89%), mostly because of HCV (46%). At study‐baseline (10 years post‐LT), 29% were obese and AH, diabetes, dislypidemia, and CRD were present in 75%, 30%, 42%, and 36%, respectively. In most cases, these complications were already present 1 year post‐LT; less than one quarter developed them onward. The 6 year cumulative survival since baseline reached 84% (n = 24 deaths), with most deaths related to recurrent graft diseases (mostly HCV) followed by de novo tumors or CVE. 1, 3, 5 and 10 years cumulative rates of CVE and de novo tumors since baseline were 2%, 5%, 10% and 17%, and 1%, 3%, 6% and 13%, respectively. Chronic renal impairment was independently associated with survival and development of CVE since baseline. The medium‐term survival of ‘long‐term survivors’, i.e. patients alive 10 years after LT is good, but metabolic complications and CRD are common and continue to increase afterwards. Cardiovascular events and de novo tumors increase gradually over time and represent a major cause of late mortality.

Indications for and Results of Liver Retransplantation

Liver retransplantation (LReTx) is the therapeutic option for the irreversible failure of a hepatic graft. Our aim was to evaluate the rate of and indications for LReTx and actuarial patient survivals. Among 1260 LTx were 79 LReTx (6.3%). During the first LTx, there were no apparent differences between patients who did or did not required LReTx. The most frequent reasons were hepatic artery thrombosis (31.6%), recurrence of the VHC cirrhosis (30.4%), and primary graft failure (21.5%). The actuarial survivals at 1 and 5 years were 83% and 69% among those without LReTx versus 71% and 61% among early LReTx, and 64% and 34% among late LReTx (P < .001). Although there exists high morbidity and mortality with LReTx, it seems that this therapeutic alternative continues to be valid for patients with early hepatic loss, but not when the graft loss was late. It becomes necessary to define the minimal acceptable results that patient can benefit from LReTx.

Step-by-step isolated resection of segment 1 of the liver using the hanging maneuver

The caudate lobe can be the origin of primary liver tumours or the sole site of liver metastases. This lobe is anatomically divided into 3 parts: Spiegels lobe (Couinauds segment 1), paracaval portion (Couinauds segment 9), and the caudate process. In this series of 4 cases, we provide a step-by-step description of a surgical technique variation that can be applied to resections of lesions localized in segment 1. We believe that other than size, lesion removal in this hepatic anatomic area, which is difficult to perform, can be done more easily using this new approach because it requires minimal mobilization without unnecessary parenchyma transection of other liver parts. Therefore, it reduces the risk of lesions in the inferior vena cava and the middle hepatic vein and respects adequate margins without the use of clamping maneuvers and in an acceptable surgical time.

Low RNA translation activit limits the efficacy of hydrodynamic gene transfer to pig liver in vivo

Hydrodynamic gene delivery has proved an efficient strategy for nonviral gene therapy in the murine liver but it has been less efficient in pigs. The reason for such inefficiency remains unclear. The present study used a surgical strategy to seal the whole pig liver in vivo.

Role of resection surgery in breast cancer liver metastases. Experience over the last 10 years in a reference hospital

Abstract Introduction Breast cancer liver metastases (BCLM) are considered as a systemic disease which is mainly treated with chemotherapy, while the role of surgical resection still remains to be well defined. The aim of the study is to analyse the survival and prognostic factors predictive of mortality in patients with BCLM treated by liver resection. Material and methods A total of 21 patients were operated on between 1998–2008, with liver resection being performed on 12. We retrospectively collected several variables. Results The mean age was 48 years. The most frequent stage was I, with curative surgery in all cases, and the majority (66.7%) received adjuvant treatment. The BCLM were mainly meta metachronic (83.3%). The majority (66.7%) received neoadjuvant treatment. The liver resection was R0 in all cases with no morbidity and a mortality in the long term of 8.3%. Two-thirds received chemotherapy. The estimated survival at one year was 67% and 23% at 5 years. A disease free period of less than 24 months between the primary tumour and the appearance of metastasis was associated with a worse survival. Conclusions Resection of BCLM within a multimodal treatment is safe in selected patients.

Framingham score, renal dysfunction, and cardiovascular risk in liver transplant patients

Cardiovascular (CV) events represent major impediments to the long‐term survival of liver transplantation (LT) patients. The aim of this study was to assess whether the Framingham risk score (FRS) at transplantation can predict the development of post‐LT cardiovascular events (CVEs). Patients transplanted between 2006 and 2008 were included. Baseline features, CV risk factors, and CVEs occurring after LT (ischemic heart disease, stroke, heart failure, de novo arrhythmias, and peripheral arterial disease) were recorded. In total, 250 patients (69.6% men) with a median age of 56 years (range, 18‐68 years) were included. At transplantation, 34.4%, 34.4%, and 33.2% of patients, respectively, had a low, moderate, and high FRS with a median FRS of 14.9 (range, 0.09‐30); 14.4% of LT recipients developed at least 1 CVE at a median of 2.619 years (range, 0.006‐6.945 years). In the univariate analysis, factors associated with the development of CVEs were the continuous FRS at LT (P = 0.003), age (P = 0.007), creatinine clearance [estimated glomerular filtration rate (eGFR); P = 0.020], and mycophenolate mofetil use at discharge (P = 0.011). In the multivariate analysis, only the eGFR [hazard ratio (HR), 0.98; 95% confidence interval (CI), 0.97‐1.00; P = 0.009] and FRS (HR, 1.06; 95% CI, 1.02‐1.10; P = 0.002) remained in the model. Moreover, an association was also found between the FRS and overall survival (P = 0.004) with 5‐year survival rates of 82.5%, 77.8%, and 61.4% for the low‐, moderate‐, and high‐risk groups, respectively. Continuous FRS, eGFR, and hepatitis C virus infection were independent risk factors for overall mortality. In our series, the FRS and eGFR at LT were able to predict the development of post‐LT CVEs and poor outcomes. Liver Transpl 21:812‐822, 2015.