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Liver transplant (LT) is the primary treatment for patients with end-stage liver disease. About 25000 LTs are performed annually in the world. The potential for intraoperative bleeding is quite variable. However, massive bleeding is common and requires blood transfusion. Allogeneic blood transfusion has an immunosuppressive effect and an impact on recipient survival, in addition to the risk of transmission of viral infections and transfusion errors, among others. Techniques to prevent excessive bleeding or to use autologous blood have been proposed to minimize the negative effects of allogeneic blood transfusion. Intraoperative reinfusion of autologous blood is possible through previous self-donation or blood collected during the operation. However, LT does not normally allow autologous transfusion by prior self-donation. Hence, using autologous blood collected intraoperatively is the most feasible option. The use of intraoperative blood salvage autotransfusion (IBSA) minimizes the perioperative use of allogeneic blood, preventing negative transfusion effects without negatively impacting other clinical outcomes. The use of IBSA in patients with cancer is still a matter of debate due to the theoretical risk of reinfusion of tumor cells. However, studies have demonstrated the safety of IBSA in several surgical procedures, including LT for hepatocellular carcinoma. Considering the literature available to date, we can state that IBSA should be routinely used in LT, both in patients with cancer and in patients with benign diseases., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest to disclose.

Background: Reliable measurement of basal energy expenditure (BEE) in liver transplant (LT) recipients is necessary for adapting energy requirements, improving nutritional status and preventing weight gain. Indirect calorimetry (IC) is the gold standard for measuring BEE. However, BEE may be estimated through alternative methods, including electrical bioimpedance (BI), Harris-Benedict Equation (HBE), and Mifflin-St. Jeor Equation (MSJ) that carry easier applicability and lower cost., Aim: To determine which of the three alternative methods for BEE estimation (HBE, BI and MSJ) would provide most reliable BEE estimation in LT recipients., Methods: Prospective cross-sectional study including dyslipidemic LT recipients in follow-up at a 735-bed tertiary referral university hospital. Comparisons of BEE measured through IC to BEE estimated through each of the three alternative methods (HBE, BI and MSJ) were performed using Bland-Altman method and Wilcoxon Rank Sum test., Results: Forty-five patients were included, aged 58±10 years. BEE measured using IC was 1664±319 kcal for males, and 1409±221 kcal for females. Average difference between BEE measured by IC (1534±300 kcal) and BI (1584±377 kcal) was +50 kcal (p=0.0384). Average difference between the BEE measured using IC (1534±300 kcal) and MSJ (1479.6±375 kcal) was -55 kcal (p=0.16). Average difference between BEE values measured by IC (1534±300 kcal) and HBE (1521±283 kcal) was -13 kcal (p=0.326). Difference between BEE estimated through IC and HBE was less than 100 kcal for 39 of all 43patients., Conclusions: Among the three alternative methods, HBE was the most reliable for estimating BEE in LT recipients., Competing Interests: none

Arterial conduits are necessary in nearly 5% of all liver transplants and are usually constructed utilizing segments of donor iliac artery. However, available segments of donor iliac artery may not be lengthy enough or may not possess enough quality to enable its inclusion in the conduit. Although there are few reports of arterial conduits constructed solely utilizing prosthetic material, no previous reports of conduits composed of a segment of donor iliac artery and prosthetic material (mixed biologic and synthetic arterial conduits) were found in the medial literature to date. Two cases reporting successful outcomes after creation of mixed biologic and prosthetic arterial conduits are outlined in this report. Reason for creation of conduits was complete intimal dissection of the recipient's hepatic artery in both cases. In both cases, available segments of donor iliac artery were not lengthy enough to bridge infrarenal aorta to porta hepatis. Both patients have patent conduits and normally functioning liver allografts, respectively, at 4 and 31 months after transplant. Mixed biologic and synthetic arterial conduits constitute a viable technical option and may offer potential advantages over fully prosthetic arterial conduits.

Background. Transarterial chemoembolization alone or in association with radiofrequency ablation is an effective bridging strategy for patients with hepatocellular carcinoma awaiting for a liver transplant. However, cost of this therapy may limit its utilization. This study was designed to evaluate the outcomes of a protocol involving transarterial embolization, percutaneous ethanol injection, or both methods for bridging hepatocellular carcinomas prior to liver transplantation. Methods. Retrospective review of all consecutive adult patients who underwent a first liver transplant as a treatment to hepatitis C-related hepatocellular carcinoma at our institution between 2002 and 2012. Primary endpoint was patient survival. Secondary endpoint was complete tumor necrosis. Results. Forty patients were analyzed, age 58 ± 7 years. There were 23 males (57.5%). Thirty-six (90%) out of the total 40 patients were within Milan criteria. Complete necrosis was achieved in 19 patients (47.5%). One-, 3-, and 5-year patient survival were, respectively, 87.5%, 75%, and 69.4%. Univariate analysis did not reveal any variable to impact on overall patient survival. Conclusions. Transarterial embolization, ethanol injection, or the association of both methods followed by liver transplantation comprises effective treatment strategy for hepatitis C-related hepatocellular carcinoma. This strategy should be adopted whenever transarterial chemoembolization and/or radiofrequency ablation are not available options.

Purpose: According to the current criteria, the diagnosis of early allograft dysfunction usually cannot be established before the end of the first week after liver transplantation. Thus, early predictive tests for detecting allograft dysfunction are still warranted to prevent allograft failure. This study was undertaken to assess the role of low serum factor V activity as an early prognostic factor (postoperative day 2) after liver transplantation., Methods: A retrospective review of all consecutive adult patients who underwent first orthotopic whole-graft liver transplant at our institution between March 2002 and June 2011 was undertaken. Primary endpoint was graft failure within 90 days after transplantation., Results: Of all 105 patients analyzed in this study, 39 (37.1 %) were female and 66 (62.9 %) were male. Mean age was 52.7 ± 11.7 years, and median follow-up period was 2474 ± 164 days. There were overall 33 (31.4 %) deaths, 13 of those occurring on the first 90 post-transplant days. Multivariate analysis demonstrated that serum factor V lower than 41.5 % and female gender had a negative impact not only on allograft failure/death within 90 days after transplantation (RR = 5.30, CI = 1.40-20.2, p = 0.015 and RR = 5.23, CI = 1.53-21.33, p = 0.008) but also on overall mortality. For prediction of allograft failure/death occurring during the first 3 months, serum factor V level of 41.5 % or lower exhibited a specificity of 87.9 %, a sensitivity of 42.9 %, an accuracy of 81.9 %, a positive predictive value of 35.3 %, and a negative predictive value of 90.9 %., Conclusions: Assessment of serum factor V levels on postoperative day 2 might be a promising prognostic tool for early prediction of inferior outcomes after liver transplantation.

Organs from deceased donors with traumatic abdominal injury, peritoneal contamination and open abdomen are usually discarded due to risks of transmission of severe infections to the recipient. There are no specific recommendations regarding organ utilization from these donors, but they might be an unexplored source able to attenuate organ shortage. Herein, the first successful report of a case involving liver transplantation using a liver allograft procured from a deceased donor with an open abdomen is outlined. This donor was a young trauma patient in which peritoneal contamination had occurred following a gunshot wound. Also included in this the report is liver transplant from a donor, who also was a trauma victim with an enteric perforation. The decision-making process to accept liver allografts from donors with a greater risk of peritoneal infection involved the absence of uncontrolled sepsis or visible contamination of the cavity. Appropriate donor-recipient matching and adequate anti-infectious management might have contributed to a favorable outcome, which suggest that these donors can be used as alternatives to reduce organ shortage.

Transarterial chemoembolization (TACE) and transarterial embolization (TAE) have improved the survival rates of patients with unresectable hepatocellular carcinoma (HCC); however, the optimal TACE/TAE embolic agent has not yet been identified. The aim of this study was to compare the effect of two different embolic agents such as microspheres (ME) and polyvinyl alcohol (PVA) on survival, tumor response, and complications in patients with HCC submitted to transarterial embolization (TAE). Eighty HCC patients who underwent TAE between June 2008 and December 2012 at a single center were retrospectively studied. A total of 48 and 32 patients were treated with PVA and ME, respectively. There were no significant differences in survival (P = 0.679) or tumoral response (P = 0.369) between groups (PVA or ME). Overall survival rates at 12, 18, 24, 36, and 48 months were 97.9, 88.8, 78.9, 53.4, and 21.4% in the PVA-TAE group and 100, 92.9, 76.6, 58.8, and 58% in the ME-TAE group (P = 0.734). Patients submitted to TAE with ME presented postembolization syndrome more frequently when compared with the PVA group (P = 0.02). According to our cohort, the choice of ME or PVA as embolizing agent had no significant impact on overall survival.

Background: The mechanisms involved in organ protection by volatile anaesthetics are not completely understood. In the liver transplant setting, there is a lack of information in the literature about whether sevoflurane anaesthesia has a superior hepatoprotective effect when compared with isoflurane., Objective: To compare the antioxidant and protective effects of isoflurane and sevoflurane., Design: A randomised, comparative, experimental study., Setting: The study was performed in the Animal Experimentation Unit of Hospital de Clínicas de Porto Alegre, Brazil. Twenty male Wistar rats weighing between 350 and 450 g were randomly assigned to one of two groups., Intervention: Each group consisted of 10 animals that were exposed to one of two different volatile anaesthetics (sevoflurane or isoflurane). In both groups, five rats were used as 'donors' and another five as 'recipients'. In order to evaluate the effects of each anaesthetic agent, the same anaesthetic technique was used during procurement and reperfusion operations., Main Outcome Measures: Samples of the preservation solution were collected during cold ischaemia to measure aminotransferase and lactate dehydrogenase (LDH) concentrations. After 15 min of reperfusion, blood samples were taken to measure the levels of aminotransferases, LDH and thiobarbituric acid reactive substances (TBARS). The concentrations of TBARS, catalase and nitric oxide derivatives were measured in the liver tissue after reperfusion., Results: Rats in the sevoflurane group had significantly lower concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and LDH in the samples obtained from the preservative solution after 6 h of cold ischaemia (P < 0.05). Serum TBARS concentrations were significantly lower in the group exposed to sevoflurane anaesthesia (P < 0.001). There were no significant differences in the tissue concentrations of TBARS and catalase (P = 0.089 and P = 0.24, respectively). However, the concentration of nitric oxide was significantly higher in the liver tissue of the rats exposed to sevoflurane anaesthesia (P < 0.05)., Conclusion: These results suggest that sevoflurane anaesthesia seems to have superior protective and antioxidant effects to isoflurane anaesthesia, not only during cold preservation but also in the early phase of liver reperfusion.

Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication associated with the transplant recipient. We chronicle a case of PTLD in a failed graft presenting as a small bowel obstruction in a pancreas-only transplant patient. While typical symptoms may be elusive in the complex immunosuppressed patient, graft pain along with persistent graft pancreatitis and a positive Epstein-Barr viremia should raise suspicion for an underlying PTLD.

Background: Long-term insulin independence after islet transplantation depends on engraftment of a large number of islets. However, the yield of pancreatic islets from brain-dead donors is negatively affected by the up-regulation of inflammatory mediators. Brain death is also believed to increase tissue factor (TF) expression, contributing to a low rate of engraftment., Methods: We conducted a case-control study to assess brain death-induced inflammatory effects in human pancreas. Seventeen brain-dead patients and 20 control patients undergoing pancreatectomy were studied. Serum tumor necrosis factor (TNF), interleukin (IL) 6, IL-1β, interferon (IFN) γ, and TF were measured using enzyme-linked immunosorbent assay kits. Gene expressions of these cytokines and TF were evaluated by reverse transcriptase quantitative polymerase chain reaction. Protein quantification was performed by immunohistochemistry in paraffin-embedded pancreas sections., Results: Brain-dead patients had higher serum concentrations of TNF and IL-6 and increased TNF protein levels compared to controls. The groups had similar TNF, IL-6, IL-1β, and IFN-γ messenger RNA levels in pancreatic tissue. Reverse transcriptase quantitative polymerase chain reaction revealed TF messenger RNA up-regulation in controls. Immunohistochemical analyses showed that brain-dead patients had increased TNF protein levels compared to controls., Conclusions: Brain death induces inflammation evidenced by the up-regulation of TNF in serum and pancreatic tissue. Blocking the expression of key inflammatory mediators in brain-dead donors should be evaluated as a new approach to improve the outcomes of islet transplantation.

Anti-reflux barrier (ARB) resistance may be useful to test new treatments for gastroesophageal reflux (GER). The ARB has been estimated by increasing gastric yield pressure (GYP) and gastric yield volume (GYV) in animal models but has not been validated. This study aimed to develop an experimental model suitable for assessing the ARB resistance to increasing intragastric pressure and volume and its reproducibility in a seven-day interval. Ten two-month-old female Large-White swine were studied. Intragastric pressure and volume were recorded using a digital system connected to a Foley catheter inserted through gastrostomy into the stomach. GYP and GYV were defined as the gastric pressure and volume able to yield gastric contents into the esophagus detected by esophageal pH. A sudden pH drop below 3 sustained during 5 min was considered diagnostic for gastric yield. Animals were studied again after seven days. On days 0 and 7, there were no significant differences for GYP (mean ± SD = 7.66 ± 3.02 mmHg vs. 7.07 ± 3.54 mmHg, p = .686) and GYV (636.70 ± 216.74 ml vs. 608.30 ± 276.66 ml; p = .299), respectively. Concordance correlation coefficient (ρc) was significant for GYP (ρc = 0.634, 95% CI = 0.141-0.829, p = .006), but not for GYV (ρc = 0.291, 95% CI = -0.118 to 0.774, p = .196). This study demonstrated an experimental model, assessing the ARB resistance. GYP seems to be a more reliable parameter than GYV for assessment of ARB resistance.

Background: Fructose 1,6-biphosphate (FBP) has been shown to exert therapeutic effects in models of ischemia-reperfusion in organs other than the liver. This study compared FBP and University of Wisconsin (UW) solution during cold storage and reperfusion, among mitochondria of adult male Wistar rat livers., Methods: Adult male Wistar rats were assigned to two groups according to the preservation solution used; UW or FBP Aspartate transaminase (AST), alanine transferase (ALT); and lactic dehydrogenase (LDH) were measured in samples of the storage solution obtained at 2, 4 and 6 hours of preservation. After 6 hours of cold storage, we reperfused the liver, taking blood samples to measure AST, ALT, LDH, and throbarbituric acid reactive substances (TBARS). Hepatic fragments were processed for histologic analysis; for determinations of TBARS, catalase, and nitric oxide as well as for mitochondrial evaluation by infrared spectroscopy., Results: During cold preservation, levels of AST and LDH in the storage solution were lower among the FBP group, but after reperfusion, serum levels of AST, ALT, and LDH were higher in this group, as was catalase activity. TBARS and nitric oxide were comparable between the groups. In the UW group there was a higher amide I/amide II ratio than in the FBP group, suggesting an abnormal protein structure of the mitochondrial membrane. No signs of preservation injury were observed in any liver biopsy, but sinusoidal congestion was present in livers preserved with FBP., Conclusion: FBP showed a protective effect for preservation during cold storage seeming to protect the mitochondrial membrane although it did not prevent reperfusion injury., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To study the expression of heme-oxygenase-1 (HO-1), an enzyme induced by oxidative stress, in specimens obtained from an experimental model in rats that evaluated the role of gastric and duodenal reflux in esophageal carcinogenesis., Methods: Esophageal specimens embedded in paraffin obtained from different experimental groups of rats were used for immunohistochemistry analysis of HO-1 expression. The rats had been divided into the following groups and were killed after 22 weeks: (1) cardioplasty to induce acid reflux; (2) esophagoduodenal anastomosis to induce duodenal reflux; (3) no treatment; (4) cardioplasty + diethylnitrosamine (DEN); (5) esophagoduodenal anastomosis + DEN; and (6) DEN. The study sample comprised 3 specimens from each group with the most severe histopathological lesions found on each study branch., Results: The expression of HO-1 was seen only in rat specimens submitted to esophagoduodenal anastomosis (Groups 2 and 5), and the analysis of mean fluorescence intensity revealed a significant increase of HO-1 expression (4.8 and 4.6 fold, respectively) when compared with the control group (Group 3) (p<0.05). The main target for HO-1 induction was the inflammatory cells inside the tumor or in subepithelial areas. Rats exposed to gastric reflux had no HO-1 expression., Conclusion: Reflux esophagitis induced by reflux of duodenal contents, which provoked considerable oxidative stress, may play an important role in esophageal carcinogenesis. Acid reflux did not induce oxidative stress in this experimental model.

Background and Aims: Endoscopic augmentation of the esophagogastric junction (EGJ) with polymethylmethacrylate (PMMA) has been reported in an experimental short-term study. We assessed whether endoscopic augmentation of the EGJ with PMMA is durable, safe, and efficacious after 6 months in mini-pigs., Methods: Ten mini-pigs were studied under anesthesia. After a pilot study in two animals, eight mini-pigs underwent lower esophageal sphincter (LES) manometry and gastrostomy with measurement of gastric yield volume (GYV) and gastric yield pressure (GYP). Endoscopic implantation of PMMA was performed aiming for the submucosa of the EGJ. Six months later, LES manometry and GYV and GYP measurements were repeated and animals were sacrificed, followed by microscopic analyses of the EGJ., Results: Out of 32 implants (four per animal), 29 (91%) were identified as submucosal nodules postmortem. PMMA deposits were found at microscopic analysis in all animals and located as follows [mean (range)]: submucosa 61.5% (37.5-91%), muscularis propria 21.5% (0-58%), mucosa 11% (0-25%), and subserosa 6% (0-17%). Neither esophageal perforation nor death was observed. A significant increase in GYV (1,404 versus 905 ml; p = 0.02) and a borderline increase in GYP (8.1 versus 6.5 mmHg; p = 0.057) were detected 6 months later., Conclusions: Endoscopic augmentation of the esophagogastric junction with PMMA was durable and had no complications after 6 months. However, the occurrence of implants in the subserosa requires technical refinement before use in clinical trials.

Background and Aims: Endoscopic injection of filler agents into the esophagogastric junction has been developed to augment the antireflux barrier and decrease gastroesophageal reflux (GER). However, evidence of efficacy is lacking and serious complications have been reported in humans. The aim of this study was to assess whether endoscopic implantation of polymethylmethacrylate augments the antireflux barrier in a porcine model for GER., Methods: Large White pigs underwent esophageal manometry, gastric yield pressure (GYP), and gastric yield volume (GYV) measurements and implantation of PMMA in the distal esophagus under general anesthesia. After follow-up of 28 days, esophageal manometry and gastric yield measurements were repeated and animals sacrificed., Results: Implantation of PMMA was performed in 18 animals, and 14 animals survived 28 days. There was a significant increase in GYP (10.7 mmHg versus 8.1 mmHg; p = 0.017) and GYV (997 ml versus 393 ml; p < 0.001) after PMMA implantation, whereas resting LES pressure did not change significantly. Acute inflammatory changes and fibrous tissue deposits were found surrounding the PMMA implants during histology. One animal died after esophageal perforation and three others due to pneumonia (two) and colon perforation (one) in the postoperative period., Conclusions: Endoscopic implantation of PMMA in the distal esophagus augments the antireflux barrier 28 days after the procedure. However, esophageal perforation points to the need for technical refinements to make the procedure safer.

Isolated liver perfusion has been used to evaluate the beneficial effects of several agents. In the present study, we developed a model using a recipient rat to reperfuse harvested livers in an ex situ, in vivo recirculating system. A total of 25 reperfusion procedures using adult male Wistar rats as donors and recipients were done. The preservation of the livers was performed with University of Wisconsin solution for 6 hours. Thereafter, the liver was reperfused with blood from another rat. We believe that the model presented herein offers an alternative method to evaluate early hepatocellular damage or hepatic microcirculation.

Very large right-sided liver tumors may grow up to the base of the umbilical fissure and involve the left hepatic duct and can occasionally reach the bile duct confluence. This kind of involvement has often been considered a contraindication to resection. We report a patient who presented with a large hepatic metastasis from colorectal cancer that reached the umbilical fissure and involved the left hepatic duct just above the bile duct confluence. An extended right hepatectomy including complete resection of caudate lobe was performed. We resected the left and common hepatic ducts, as well as both the entire hepatic and the proximal third of common bile duct. A long jejunal limb Roux-en-Y (45 cm) single-layer left intrahepatic hepaticojejunostomy was constructed. She is still well 14 months postoperatively. To the best of our knowledge, this is the first report of such a procedure employed for the treatment of a liver metastasis from colorectal cancer. Extended right hepatectomy including complete caudate lobe resection can be feasible even when the majority of the extrahepatic biliary system needs to be resected. Our approach probably offers the only chance to prevent early death from liver failure in these patients.

Background: Celiac disease is a gluten-induced disease of global malabsorption. There is a subset of patients with celiac disease who are free of major symptoms but who have typical damage to the intestinal mucosa (silent disease). We present the case of a 50-year-old white woman with no clinical symptoms of celiac disease who developed diarrhea and weight loss 12 weeks after a pancreatoduodenectomy for ampullary cancer., Methods: Microbiological and biochemical examination of the feces did not provide clues useful to diagnosis, and diarrhea was not affected by pancreatic enzyme replacement or administration of antiperistaltic drugs., Results: Review of the pathologic specimen and blood tests were compatible with celiac disease., Conclusion: This clinical scenario illustrates that subclinical celiac disease may be an underdiagnosed cause of malabsorption after major upper gastrointestinal surgery and should be considered in the differential diagnosis of diarrhea after pancreatoduodenectomy.

It is known that some nitrosamines preferably affect particular organs because of their organospecificity. Diethylnitrosamine (DEN) is one of the most powerful nitrosamines for experimentally inducing esophagus cancer. The present study aimed to evaluate the rate and type of epithelial lesions induced by DEN in mice. We also assessed the role of alcohol and N-nitrosonornicotine (NNN) as promoters of this carcinogenesis. A total of 208 female mice (Mus musculus) were allocated to five experimental groups: group 1, water only (controls); group 2, DEN + water; group 3, DEN + NNN; group 4, DEN + 6% alcohol solution; group 5, DEN + NNN + 6% alcohol solution. Animals in groups 2, 3, 4 and 5 received DEN (0.04 ml/l) three times per week, and during the following 4 days they received the other solutions. NNN was provided at a final concentration of 30 mg/l. The overall experimental period was 180 days. At the end of this time, the animals were killed and their esophagus was dissected for macro- and microscopic analysis. There was no significant difference in relation to the size of the esophagus and to the average DEN intake by the animals (p > 0.05). A statistically significant difference (p < 0.0001) was observed between controls and all other experimental groups. There was no significant difference among experimental groups treated with carcinogens (p > 0.05). The average incidence of cancer was 85.4%. The experimental model used in the present study is a very potent indicator of esophagus cancer. Owing to the high incidence for cancer observed in the present study, it was not possible to assess the effect of alcohol and NNN as inducers for the development of esophageal cancer.