Constantino Fondevila

The number of patients suitable for liver transplantation is progressively increasing due to the excellent results achieved with this procedure, giving rise to a growing imbalance in the number of candidates on the waiting list and the number of donors. This situation has prompted transplant teams to search for alternatives to increase the number of liver grafts. On the one hand, the criteria for donation have been broadened to include donors with advanced age, liver steatosis, hepatitis B and C viruses, neoplasms, and benign underlying diseases. On the other hand, new transplant techniques have been used with grafts from split livers, living donors, sequential or domino transplants and non-heart-beating donors. Other options such as xenotransplantation and hepatocyte transplants currently lack clinical applicability.

We investigated the effects of the connecting segment-1 (CS1) peptide, which blocks fibronectin (FN)-α4β1 integrin interactions upon cell signaling, leukocyte migration, and secretion of proinflammatory cytokines, in a well-established steatotic rat liver model using ex vivo cold ischemia followed by isotransplantation. In this model, CS1 peptides were administered through the portal vein of steatotic Zucker rat livers prior and after cold ischemic storage. Lean Zucker recipients of fatty orthotopic liver transplantation (OLT) received an additional 3-day course of CS1 peptides post-OLT. CS1 peptide-treated steatotic OLTs harvested at 1, 3, and 7 days showed moderated levels of p42/44 mitogen-activated protein kinase (MAPK) phosphorylation, comparable to those observed in steatotic naïve livers. In contrast, p42/44 MAPK phosphorylation was found up-regulated in 1- to 3-day damaged control OLTs. However, 7-day control OLTs were characterized by virtually lack of p42/44 MAPK phosphorylation. Lack of p42/44 MAPK phosphorylation in 7-day control OLTs was correlated with massive presence of leukocytes in the grafts and elevated levels of proinflammatory cytokines. CS1 peptide-treated OLTs at 7 days showed a profound decrease in T-cell (10 ± 3 vs 56 ± 20, P < .03) and monocyte/macrophage (+/++ vs +++) infiltration and significantly reduced levels of cytokine expression, such as IL-2 (approximately sixfold), and IFN-γ (approximately three- to fourfold), as compared with controls.

The aim of this study was to evaluate a consecutive series of 1000 liver transplants performed in our institution and to evaluate changes over time in donors and recipients, as well as results.MATERIAL AND METHOD: To clearly evaluate the differences between the initial transplantation period and the present period, the first 100 consecutive liver transplantations performed (June 1988-June 1990) and the last 200 consecutive liver transplantations performed (January 2001-June 2003) were compared.RESULTS: Donor age increased (23+/-10 vs. 45+/-19), the etiology of brain death changed (severe head injury: 78% vs. 23.5%; stroke: 17% vs. 52.5%) and the percentage of donors from alternative methods to cadaveric donors increased (living donors: 12.5%) in the second period. Regarding recipients, the piggy-back technique and biliary anastomosis without T-tube were introduced in the second period. Actuarial 1-year survival was higher in the second period than in the first (84% vs. 91.3%). The need for retrasplantation in the entire series was 9.5%, with actuarial survival at 1, 5 and 10 years of 67.7%, 51.3% and 39.4%, respectively.CONCLUSION: Because of the lack of donors and the greater number of patients on the waiting list, poorer quality donors and more critical recipients have been accepted and alternative and innovative programs have been started. Nevertheless, due to improvement in patient management before, during and after transplantation, the previous good results have been maintained.

Hiliar cholangiocarcinoma is the most common type of cholangiocarcinoma, an represent around 10% of all hepatobiliary tumors. It is an aggressive malignancy, resectable in around 47% of the patients at diagnosis. Complete resection is the most effective and only potentially curative therapy, with a survival rate of less than 12 months in unresectable cases. Axial computerized tomography and magnetic resonance are the most useful image techniques to determine the surgical resectability. Clinically, jaundice and pruritus are the most common symptoms at diagnosis;preoperative biliary drainage is recommended using endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography. Surgery using extended liver resections with an en bloc resection of the liver with vascular reconstruction is the technique with the highest survival. Complete resection with histologically negative resection margins (R0), nodal involvement and metastases are the most important prognostic factors.

ABSTRACT Introduction Hilar cholangiocarcinoma involves the bifurcation of the main bile duct. The prognosis of this patients is very poor and only radical surgery can increase the survival rates. However, it is mandatory to obtain a negative resection margins, defined as the absence of any macroscopic or microscopic evidence of cancer including carcinoma in situ and severe atypia. Due to its localization and its propensity for local invasion, this tumor often involves the portal vein, hepatic arteries and liver parenchyma. Methods We report two diagnosed patients with hilar cholangiocarcinoma involving the portal vein treated by curative surgery. Results In both cases the radical resection included the portal vein and two cryopreserved arterial allografts were used to reconstruct the vein continuity. The postoperative follow-up has been satisfactory without thrombosis and adequate liver function. No evidence of recurrence has been detected after 7 and 4 months, respectively, but in the first case an elevation of CA 19.9 in serum exists. Conclusions It is feasible to perform curative surgery in hilar cholangiocarcinoma involving the portal vein. In cases of extensive resection, it is useful to use cryopreserved arterial allografts to reconstruct the vascular continuity.

It has been suggested that vascular stasis during cardio-circulatory arrest leads to the formation of microvascular thrombi and the viability of organs arising from donation after circulatory determination of death (DCDD) donors may be improved through the application of fibrinolytic therapy. Our aim was to comprehensively study the coagulation profiles of Maastricht category II DCDD donors in order to determine the presence of coagulation abnormalities that could benefit from fibrinolytic therapy. Whole blood from potential DCDD donors suffering out-of-hospital cardiac arrest was sampled after declaration of death in the emergency department, and rotational thromboelastomeric analysis was performed. Between July 2012 and December 2013, samples from 33 potential DCDD donors were analyzed. All patients demonstrated hyperfibrinolysis (HF), as reflected by maximum clot lysis of 98-100% in all cases, indicating that there is no role for additional fibrinolytic therapy in this setting. A...

Ischemia/reperfusion injury (IRI) is a multifactorial antigen-independent process that affects both early and late graft function after transplantation. The complex mechanism of IRI can be attributed to neutrophil accumulation at the site of tissue injury, release of pro-inflammatory mediators such as oxygen free radicals (OFRs), and cytokines, which lead to cellular injury that culminates in the ultimate graft failure. The heme oxygenase-1 (HO-1) system is among the most critical of cytoprotective mechanisms activated during the cellular stress. The cytoprotection often seen in the transplanted organ following local HO-1 overexpression may include several factors, such as: a) antioxidant function, b) maintenance of microcirculation, c) anti-apoptotic function, and d) anti-inflammatory function. The role of enhanced endogenous HO-1 overexpression, and HO-1 downstream mediators (bilirubin, ferritin, CO), which protect against the IRI sequel, remain currently one of the most active ar...

Surgical resection is the only curative treatment of pancreatic carcinoma (PC). An accurate assessment of the extension of PC is mandatory to select appropriate patients to this therapeutic option. This study was aimed at assessing the usefulness of abdominal ultrasonography (US) and computed tomography (CT) to establish tumoral staging and to predict tumor resectability. Between January 1990 and December 1995, 84 PC patients were submitted to surgical procedures (potentially curative resection in 30%, biliodigestive anastomosis in 51% and exploratory laparotomy in 13%). Preoperative staging was carried out by means of abdominal US and/or CT. Definitive staging was established according to surgical findings, using the TNM classification. Accuracy of preoperative evaluation with regard to tumoral staging was 65%, being underestimated in 29 (35%) patients. This underestimation was mainly due to lesions in stage I. In addition, preoperative staging predicted tumor unresectability with ...

Donation after circulatory determination of death (DCD) has the potential to increase the applicability of transplantation as a treatment for end-stage organ disease; its use is limited, however, by the warm ischemic damage suffered by potential grafts. Abdominal regional perfusion (ARP) has been employed in this setting to not only curtail the deleterious effects of cardiac arrest by re-establishing oxygenated flow but also test and even improve the viability of the kidneys and liver prior to transplantation. In the present review article, we discuss experimental and clinical studies that have been published to date on the use of ARP in DCD, differentiating between its application under hypothermic and normothermic conditions. In addition to describing results that have been achieved thus far, we describe the major obstacles limiting the broader implementation of ARP in this context as well as potential means for improving the effectiveness of this modality in the future.

The use of drainage after liver resection remains controversial. Data of the usefulness of drains in cirrhotic patients undergoing surgical resection are scarce. The objective of our study is to assess the usefulness of intra-abdominal drainage after liver resection for hepatocellular carcinoma in cirrhotic patients. We performed a randomized controlled trial to assess the benefits of abdominal drainage after resection of hepatocellular carcinoma in cirrhotic patients. The main end point was to compare postoperative complications and hospital stay in both groups. Abdominal drainage decreased ascites leakage and significantly reduced hospital stay in comparison to the non-drainage group. In addition, local complications were less frequent in the drainage group. Postoperative ascites leakage significantly complicated patients with clinically relevant portal hypertension. Intra-abdominal closed drainage is advisable in cirrhotic patients undergoing liver resection for hepatocellular ca...