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The Institut Georges Lopez 1 (IGL-1) solution was developed to improve the outcomes of solid organ transplantation. Nevertheless, follow-up of liver transplants using IGL-1-preserved organs is still scarce.To compare morbidity, postoperative complications, and early survival between liver grafts perfused with IGL-1 and those perfused with histidine-tryptophan-ketoglutarate (HTK) solutions.Prospective liver grafts perfused with IGL-1 (n = 65) were paired with a historical control group of recipients whose grafts were preserved with HTK solution (n = 130). The primary endpoint was the sum of the incidence of primary graft dysfunction (PGD) and primary graft nonfunction (PGNF). Secondary endpoints included resource utilization, complications, and survival analysis.In the HTK group, 52 patients (40%) exhibited either PGD or PGNF, compared to 20 patients (31%) in the IGL-1 group (P = .208). Patients from the HTK group had higher mean values for cryoprecipitate transfusion (P = .0064), first day serum lactate (P = .0099), higher incidence of vascular complications (11% vs 2% in the IGL-1 group; P = .0226), but a lower incidence of infection (7% vs 28% in the IGL-1 group; P .0001). The IGL-1 group presented a lower mean aspartate aminotransferase and alanine aminotransferase (ALT) on the first and second postoperative day and a lower ALT on the seventh day. Recipients of grafts perfused with IGL-1 had a better early survival than those whose grafts were perfused with HTK.Both solutions are safe and present good results. Grafts perfused with IGL-1 showed decreased enzymatic peaks and better short-term survival rates than the HTK group. The use of the IGL-1 solution might be preferable.

Prolonged time on the waiting list affects post-transplant survival of patients with hepatocellular carcinoma (HCC). However, it is not yet known which patients will be at higher risk for early dropout from the list. We investigate specific risk factors for early waiting list dropout in patients with HCC.This was a single-center, intention-to-treat analysis of adults with HCC, within the Milan criteria, from July 2006 through September 2013. Patients were divided into groups according to waiting list time. The main end point was dropout from the list.The dropout rates of the study cohort at 3, 6, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Patients who dropped out from the list tended to be older, with blood types A and O, and with higher Child-Pugh and Model for End-Stage Liver Disease (MELD) scores. They also had larger nodules, responded poorly to trans-arterial chemo-embolization (TACE), and had a higher alpha-fetoprotein. Those with blood types B and AB appeared to be protected for dropout (odds ratio [OR] = 0.21, P = .02). Patients who responded to TACE were also protected (OR = 0.22, P .001). When we looked into time to dropout, the only baseline characteristic that stood out was a higher MELD score (13 for those dropping out up to 90 days vs 10 for those dropping out after 180 days, P = .0025).We conclude that patients who drop out early from the list are primarily driven by the severity of liver disease. Patients who had progressive HCC had a high tumor load and poor response to loco-regional therapies, dropping out from the list after 180 days of inclusion.

There are few existing methods for shortening the decellularization period for a human-sized whole-liver scaffold. Here, we describe a protocol that enables effective decellularization of the liver obtained from pigs weigh 120 ± 4.2 kg within 72 h. Porcine livers (approx. 1.5 kg) were decellularized for 3 days using a combination of chemical and enzymatic decellularization agents. After trypsin, sodium deoxycholate, and Triton X-100 perfusion, the porcine livers were completely translucent. Our protocol was efficient to promote cell removal, the preservation of extracellular matrix (ECM) components, and vascular tree integrity. In conclusion, our protocol is efficient to promote human-sized whole-liver scaffold decellularization and thus useful to generate bioengineered livers to overcome the shortage of organs.

Introduction Ischemia–reperfusion (I/R) injury of the liver is a common area of interest to transplant and hepatic surgery. Nevertheless, most of the current knowledge of I/R of the liver derives from the hepatocyte and little is known of what happens to the cholangiocytes. Herein, we assess the sequence of early events involved in the I/R injury of the cholangiocytes. Methods Sixty Wistar rats were randomized in a SHAM group and I/R group. Serum biochemistry, histopathology, immunohistochemistry, transmission electron microscopy (TEM) and laser capture microdissection (LCM) were used for group comparison. Results There was peak of alkaline phosphatase 24 h after IR injury, and an increase of aspartate aminotransferase and alanine aminotransferase after 6 h of reperfusion, followed by a return to normal levels 24 h after injury. The I/R group presented the liver parenchyma with hepatocellular degeneration up to 6 h, followed by hepatocellular necrosis at 24 h. TEM showed cholangiocyte injury, including a progressive nuclear degeneration and cell membrane rupture, beginning at 6 h and peaking at 24 h after reperfusion. Cytokeratin-18 and caspase-3-positive areas were observed in the I/R group, peaking at 24-h reperfusion. Anti-apoptotic genes Bcl-2 and Bcl-xl activity were expressed from 6 through 24 h after reperfusion. BAX expression showed an increase for 24 h. Conclusions I/R injury to the cholangiocyte occurs from 6 through 24 h after reperfusion and a combination of TEM, immunohistochemistry and LCM allows a better isolation of the cholangiocyte and a proper investigation of the events related to the I/R injury. Apoptosis is certainly involved in the I/R process, particularly mediated by BAX.

Lymph node (LN) is a secondary lymphoid organ with highly organized and compartmentalized structure. Lymph nodes harbor B, T, and other cells among which fibroblastic reticular cells (FRCs). FRCs are characterized by both podoplanin (PDPN/gp38) expression and by the lack of CD31 expression. FRCs are involved in several immune response processes but mechanisms underlying their function are still under investigation. Double negative cells (DNCs), another cell population within LNs, are even less understood. They do not express PDPN or CD31, their localization within the LN is unknown and their phenotype and function remain to be elucidated. This study evaluates the gene expression and cytokines and chemokines profile of human LN-derived FRCs and DNCs during homeostasis and following inflammatory stimuli. Cytokines and chemokines secreted by human FRCs and DNCs partially diverged from those identified in murine models that used similar stimulation. Cytokine and chemokine secretion and their receptors expression levels differed between stimulated DNCs and FRCs, with FRCs expressing a broader range of chemokines. Additionally, dendritic cells demonstrated increased migration towards FRCs, possibly due to chemokine-induced chemotaxis since migration was significantly decreased upon neutralization of secreted CCL2 and CCL20. Our study contributes to the understanding of the biology and functions of FRCs and DNCs and, accordingly, of the mechanisms involving them in immune cells activation and migration.

Knowledge of the anatomy of the hepatic artery and its variations is important to hepatobiliary and liver transplant surgeons and interventional radiologists. We report a rare anatomic variation of liver hepatic arterial supply: a right accessory hepatic artery arising directly from the celiac trunk and observed at the time of multiorgan procurement. The anatomic variation described in this case occurs in up to 2% of cases and their knowledge is essential to avoid injuries during multiorgan procurement that could require multiple anastomoses or lead to inadvertent vessel injury. This variation is very rarely reported in the medical literature. We document successful deceased-donor liver transplantation with a graft that had an accessory right accessory hepatic artery from the celiac trunk.

Background Transplant surgeons have one the riskiest jobs in medicine. Multiple reports have described fatalities involving transplant team members who were traveling to recover organs for transplantation. There are few initiatives to use allografts recovered by local teams. We tested the impact of local organ procurement on posttransplantation survival. Methods This single-center retrospective study included primary deceased-donor liver grafts transplanted under the Model for End-stage Liver Disease system. Multivariate analysis was performed to evaluate whether liver allografts procured outside of the organ procurement organization (OPO) region were related to allograft loss. We also studied posttransplantation survival according to local procurement. Results There were 271 transplantations performed with local donors, 19 from other states, and 54 from within our state but outside of our OPO. Recipient demographic data were similar among the groups. There were more male ( P = .007), slim ( P = .01), and younger ( P = .008) donors among allografts from other states (national group). Local or regional donors had brain death more often related to cerebrovascular accidents. National donors had brain death related to trauma ( P = .01). Multivariate analysis confirmed that local organ retrieval was not related to posttransplantation survival. Kaplan-Meier curves showed no difference in patient and graft survivals among the groups. Conclusions Local procurement did not affect posttransplantation survival. Liver allografts procured by other teams showed equivalent posttransplantation outcomes. Policies that stimulate the training of local teams to procure liver allografts for distant transplant centers should be launched to increase job safety for transplant surgeons.

Intestinal transplantation has shown exceptional growth over the past 10 years. At the end of the 1990’s, intestinal transplantation moved out of the experimental realm to become a routine practice in treating patients with severe complications related to total parenteral nutrition and intestinal failure. In the last years, several centers reported an increasing improvement in survival outcomes (about 80%), during the first 12 months after surgery, but long-term survival is still a challenge. Several advances led to clinical application of transplants. Immunosuppression involved in intestinal and multivisceral transplantation was the biggest gain for this procedure in the past decade due to tacrolimus, and new inducing drugs, mono- and polyclonal anti-lymphocyte antibodies. Despite the advancement of rigid immunosuppression protocols, rejection is still very frequent in the first 12 months, and can result in long-term graft loss. The future of intestinal transplantation and multivisceral transplantation appears promising. The major challenge is early recognition of acute rejection in order to prevent graft loss, opportunistic infections associated to complications, post-transplant lymphoproliferative disease and graft versus host disease; and consequently, improve results in the long run.

Early allograft dysfunction (EAD) had been related to poor transplant outcomes during the early years of liver transplantation. We sought to determine the incidence of EAD at our unit and to evaluate its impact on posttransplant outcomes.This single-center retrospective study included primary deceased donor liver grafts transplanted under the model for end-stage liver disease system. EAD was defined as a peak values of aminotransferase2000 IU/mL during the first week or an international normalized ratio of ≥1.6 and/or bilirubin ≥10 mg/dL at day 7. The main endpoints were patient and graft survivals.Patients with versus without EAD showed similar recipient characteristics. Donors who experienced EAD who comprises 56% of recipients were heavier with larger body mass indices. EAD was an independent risk factor for allograft loss. Most retransplants were performed early due to nonfunction. The primary nonfunction rate among subjects with versus without EAD were 7% and 12% respectively (P.05). Patient survival among those with EAD was 87.4%, while without EAD it was 90% (P = NS) with graft survivals of 81.4% and 88.7% respectively (P.05).Patients with EAD show a significantly higher risk for allograft loss, but with a comparable survival after transplantation. Despite their worse outcomes, it seems that not all of these recipients behave equally.

Vascularized pancreas transplantation is the only treatment that establishes normal glucose levels and normalizes glycosylated hemoglobin levels in type 1 diabetic patients. The first vascularized pancreas transplant was performed by William Kelly and Richard Lillehei, to treat a type 1 diabetes patient, in December 1966. In Brazil, Edison Teixeira performed the first isolated segmental pancreas transplant in 1968. Until the 1980s, pancreas transplants were restricted to a few centers of the United States and Europe. The introduction of tacrolimus and mycophenolate mofetil in 1994, led to a significant outcome improvement and consequently, an increase in pancreas transplants in several countries. According to the International Pancreas Transplant Registry, until December 31st, 2010, more than 35 thousand pancreas transplants had been performed. The one-year survival of patients and pancreatic grafts exceeds 95 and 83%, respectively. The better survival of pancreatic (86%) and renal (93%) grafts in the first year after transplantation is in the simultaneous pancreas-kidney transplant group of patients. Immunological loss in the first year after transplant for simultaneous pancreas-kidney, pancreas after kidney, and pancreas alone are 1.8, 3.7, and 6%, respectively. Pancreas transplant has 10 to 20% surgical complications requiring laparotomy. Besides enhancing quality of life, pancreatic transplant increases survival of uremic diabetic patient as compared to uremic diabetic patients on dialysis or with kidney transplantation alone.

In 2006, the model for end-stage liver disease (MELD) was launched as a new liver allocation system in Sao Paulo, Brazil. We designed this study to assess the results of the new allocation policy on waiting list mortality.We reviewed the state of Sao Paulo liver transplant database from July 2003 through July 2009. Patients were divided in those who were transplanted before (pre-MELD group) and those who were transplanted after (post-MELD group) the implementation of the MELD system. Included were adult liver transplant candidates. Waiting list mortality was the primary endpoint.The unadjusted death rate in patients on the waiting list decreased significantly after the implementation of the MELD system (from 91.2 to 33.5/1000 patients/year, P.0001). Multivariate analysis has shown a significant drop of the risk of waiting list death for post-MELD patients (odds ration 0.34, P.0001).There was a reduction in waiting time and list mortality after the implementation of the MELD system in Brazil. Patients listed in the post-MELD era had a significant reduction of death risk on the waiting list. Future studies should assess posttransplant outcomes.

Introduction A new liver allocation system driven by the model for end-stage liver disease (MELD) score was implemented in Brazil in 2006. In association with the new allocation policy, there was a concomitant expansion of the number of donors. We designed this study to assess whether a potential expansion of the donor pool with these educational campaigns had reduced the severity of liver disease at transplantation. Methods We retrospectively reviewed the state of Sao Paulo liver transplant database from July 2003 through July 2009. Patients were divided into groups: those who were transplanted before (pre-MELD group) and those who were transplanted after (post-MELD group) the implementation of the MELD system. The number of transplantations and the severity of liver disease were the endpoints of the study. Results There has been a significant shift towards an older donor population, mainly those who are dying of cerebrovascular accidents. The average MELD score has changed over time. Approximately one quarter of the patients have been transplanted with a MELD score of more than 30 in the post-MELD era. However, this number has decreased over the past 3 years ( P = .012). Currently, it has been possible to transplant patients with a MELD score from 25 to 30. The number of transplantations due to hepatocarcinoma (HCC) has increased 8-fold. Conclusion An aggressive educational campaign has successfully expanded the donor pool with a concomitant yearly reduction of the average MELD score at the time of transplantation. Patients with HCC have been benefited tremendously with the new allocation system.

Introduction Since August 2010, The Brazilian National Transplantation System has allowed performance of liver transplantation (OLT) for patients with hepatocellular carcinoma (HCC) beyond the Milan criteria (MC) who have been successfully treated with preoperative downstaging (DS). Herein we sought to compare the clinical profiles and liver explant findings among patients with versus without preoperative DS. Methodology Prospective cohort of patients with HCC within and beyond the MC undergoing OLT. Patients were considered for DS if they were beyond the MC without evidence of vascular invasion or extrahepatic disease. Transcatheter arterial chemoembolization was used for DS, which was considered to be successful if the MC were achieved at any moment during the follow-up. Results Between May 2006 and May 2010, we performed 130 OLTs in HCC patients, among whom 10 received preoperative DS. Both groups were comparable for gender, age, viral etiology, serum levels of alpha fetoprotein, and Child-Pugh and Model for End-Stage Liver Disease (MELD) scores (P > .05). The liver explants were within the MC in 80% of patients with preoperative DS and 90% of those without preoperative DS. They were comparable for the number of HCC nodules, total tumor size, histologic grade, and presence of microvascular invasion. Patients with pretransplant DS showed larger HCC nodules (33.3 ± 9.65 vs 26.3 ± 9.62 mm; P .029) and more frequent macrovascular invasion (1 vs 1 patient, P = .024). Conclusion Preoperative DS for unresectable HCC may provide a curative treatment for patients who would otherwise be candidates for palliative therapy only. The baseline characteristics and liver explant findings were similar in both groups. We have yet to determine whether the differences observed regarding the size of the largest nodule and the higher frequency of macrovascular invasion have an impact on outcome.

Purpose To evaluate morphologic and pathologic features affecting therapy response in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization with doxorubicin drug eluting beads (DEB-TACE) prior to liver transplant. Materials and Methods This prospective study included 27 HCCs in 23 patients treated with DEB-TACE (DcBeads®, Biocompatibles, UK) followed by liver transplant. Imaging response was assessed with the mRECIST criteria with areas of non-enhancement used as a surrogate for necrosis. Pathology evaluation of the treated HCCs from the explanted liver was utilized to categorize the magnitude of response to the therapy: Group I, >50% necrosis, Group II, ≤50% necrosis. Pathology data included percent of necrosis after therapy, lesion size, presence of tumor capsule and presence of macro/micro-vascular invasion. Additional variables recorded included: days between DEB-TACE and transplant; number of sessions per nodule; cumulative doxorubicin dose administered to each nodule; and percentage reduction in size of each nodule after therapy. Results The mean percentage of histological necrosis identified overall was 67.8% (95% CI: 56.5%-79.4%). Group I included 18 nodules with a mean percentage of necrosis of 86.2% (60% to 100%). Group II was comprised of 9 nodules with a mean percentage of necrosis of 31.1% (15% to 40%). The mean pre-treatment lesion size by imaging was significantly larger (p=0.030) for Group I [3.2 cm (range 1.5-5.2cm)] when compared to Group II [2.1cm (range 1.5-2.5cm)]. Group I also demonstrated a significantly higher frequency of lesions having a tumor capsule compared to the Group II (p=0.0027) with a tumor capsule present in 78% and 22%, respectively. There was no significant difference between the two groups with respect to vascular invasion, time to transplantation, treatment sessions, and cumulative Doxorubicin dose and percentage reduction in size of the tumors. Conclusion Lesion size and presence of capsule around the tumor are associated with a higher percentage of necrosis after DEB-TACE.