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1.
Phys Rev Lett ; 124(6): 067201, 2020 Feb 14.
Article in English | MEDLINE | ID: mdl-32109088

ABSTRACT

The effect of compression on the magnetic ground state of Sr_{2}IrO_{4} is studied with x-ray resonant techniques in the diamond anvil cell. The weak interlayer exchange coupling between square-planar 2D IrO_{2} layers is readily modified upon compression, with a crossover between magnetic structures around 7 GPa mimicking the effect of an applied magnetic field at ambient pressure. Higher pressures drive an order-disorder magnetic phase transition with no magnetic order detected above 17-20 GPa. The persistence of strong exchange interactions between J_{eff}=1/2 magnetic moments within the insulating IrO_{2} layers up to at least 35 GPa points to a highly frustrated magnetic state in compressed Sr_{2}IrO_{4}, opening the door for realization of novel quantum paramagnetic phases driven by extended 5d orbitals with entangled spin and orbital degrees of freedom.

2.
Transplant Proc ; 50(3): 848-852, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29661451

ABSTRACT

INTRODUCTION: In hepatectomy or liver transplantation, preconditioning is a procedure indicated to protect the organ from ischemia-reperfusion injury (I-R). OBJECTIVE: Evaluate the effect of preconditioning after hepatic I-R in Wistar rats, through mitochondrial respiration, liver histology, and profile. METHOD: Twenty male Wistar rats, weighing on average 307.1 g, were anesthetized with sodium thiopental (25 mg/kg) intravenously and xylazine hydrochloride (30 mg/kg) intramuscularly. The animals were divided into 2 groups: the preconditioning group (PCG), which contained 10 animals, and the hepatic pedicle was isolated and submitted to clamping with microvascular clamp (10 minutes of ischemia and 10 minutes of reperfusion, followed by 30 minutes of ischemia and 30 minutes of reperfusion); and the simulated operation group (SOG), which contained 10 animals submitted to manipulation of the hepatic pedicle and observation for the same length of time, with blood collected for transaminase dosage measurements, and liver biopsy for evaluation of mitochondrial respiration and histologic liver analysis and after sacrificed under anesthesia. The project was approved by the Ethics Committee on Animal Experimentation CEEA/UNICAMP under protocol number 3905-1. RESULT: The PCG mitochondria showed the same respiration level as the SOG, when stimulated with the addition of adenosine diphosphate or carbonyl cyanide p-trifluoromethoxyphenylhydrazone. In the respiratory control ratio and resting of velocity of respiration the groups behaved in a similar way. The PCG presented high aspartate and alanine transaminases (P < .03) and about 60% of sinusoidal congestion and venous congestion in the histologic analysis when compared with SOG. CONCLUSION: We found that ischemia with preconditioning in Wistar rats can lead to mild histologic and biochemical dysfunction without leading to impairment of mitochondrial respiration.


Subject(s)
Ischemia/physiopathology , Ischemic Preconditioning/adverse effects , Liver/blood supply , Mitochondria/physiology , Respiration , Alanine Transaminase/blood , Animals , Carcinoma, Hepatocellular/physiopathology , Constriction , Ischemic Preconditioning/methods , Liver Circulation , Liver Neoplasms/physiopathology , Male , Random Allocation , Rats , Rats, Wistar , Reperfusion , Reperfusion Injury/physiopathology , Reperfusion Injury/prevention & control
3.
Nat Commun ; 8(1): 1203, 2017 10 31.
Article in English | MEDLINE | ID: mdl-29084943

ABSTRACT

The multifaceted character of 5f electrons in actinide materials, from localized to itinerant and in between, together with their complex interactions with 6d and other conduction electron states, has thwarted efforts for fully understanding this class of compounds. While theoretical efforts abound, direct experimental probes of relevant electronic states and their hybridization are limited. Here we exploit the presence of sizable quadrupolar and dipolar contributions in the uranium L3-edge X-ray absorption cross section to provide unique information on the extent of spin-polarized hybridization between 5f and 6d electronic states by means of X-ray magnetic circular dichroism. As a result, we show how this 5f-6d hybridization regulates the magnetism of each sublattice in UCu2Si2 and UMn2Si2 compounds, demonstrating the potentiality of this methodology to investigate a plethora of magnetic actinide compounds.

4.
Transplant Proc ; 49(4): 761-764, 2017 May.
Article in English | MEDLINE | ID: mdl-28457390

ABSTRACT

The probable reason for mixing solutions during the harvesting procedure is due to the presence of multiple transplant teams that have their own solution usage tradition. Despite numerous studies comparing the efficacy of different preservation solutions, there is no study addressing the associating solution and if there is any impact on liver graft and patient survival. The aim was to evaluate the effect of the association of preservation solutions during the harvesting procedure on liver transplantation outcomes, especially in relation to the degree of preservation injury in the postreperfusion period and patient survival. We analyzed 206 transplants that were distributed as follows: when there was association (89/206 = 43.2%) and when there was no association (117/206 = 56.8%). There was a statistically significant difference in relation to the degree of preservation injury correlated to cold ischemia time (P = .009, odds ratio 1.992; 95% confidence interval 1.185-3.347). Severe harvesting (grades III and IV) was 71.8% when the solution was not associated (P = .008). There was no difference regarding patient survival either. We found that the association of liver preservation solutions has no impact on patient survival, so it can be done safely. The best survival rate was associated with minimal harvesting.


Subject(s)
Graft Survival/drug effects , Liver Transplantation/mortality , Organ Preservation Solutions/adverse effects , Organ Preservation/methods , Adolescent , Adult , Aged , Cold Ischemia , Female , Humans , Liver/drug effects , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Survival Rate , Young Adult
5.
Transplant Proc ; 49(4): 858-862, 2017 May.
Article in English | MEDLINE | ID: mdl-28457411

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is the 6th leading cause of cancer worldwide. Its recurrence ranges from 6% to 26%. In the literature, many factors are associated with higher risk of recurrence, without a clear definition of the best method that could predict this highly lethal event. OBJECTIVE: The aim of this study was to evaluate the immunoexpression of immunohistochemical markers: HSP70, glypican 3, glutamine synthetase, and beta-catenin, as well as studying their association with tumor characteristics and prognosis of patients undergoing liver transplantation for HCC. METHODS: We studied 90 patients who underwent liver transplantation from 1998 to 2012. Afterwards we evaluated factors related to survival, tumor recurrence, and the correlation of expression of the immunohistochemical markers. RESULTS: Immunohistochemical marker glutamine synthetase showed a positive trend toward better survival. HSP70-positive patients had a higher prevalence of histologic grade III. Patients with positive glypican 3 showed larger lesions and a higher number with AFP >200 ng/mL. Patients with positive beta-catenin showed larger nodules and more with histologic grade III. The association between beta-catenin and glypican 3 showed positive association with larger nodules. CONCLUSIONS: Most of the markers studied had a correlation with at least one of the variables studied, confirming our hypothesis that these markers can indeed assist in assessing the prognosis of patients undergoing liver transplantation for HCC.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Glutamate-Ammonia Ligase/metabolism , Glypicans/metabolism , HSP70 Heat-Shock Proteins/metabolism , Liver Neoplasms/metabolism , beta Catenin/metabolism , Adult , Aged , Biomarkers/analysis , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Female , Humans , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Liver Transplantation , Longitudinal Studies , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Postoperative Period , Prognosis , Prospective Studies
6.
Transplant Proc ; 49(4): 863-866, 2017 May.
Article in English | MEDLINE | ID: mdl-28457412

ABSTRACT

BACKGROUND: Liver transplantation (LT) is a curative treatment option for hepatocellular carcinoma (HCC); recurrent HCC after liver transplantation (HCC-R) is diagnosed in 9%-16%. The objective of this study was to evaluate which factors are associated with R-HCC after liver transplantation. METHODS: This retrospective real-life study analyzed 278 LTs from 3 reference centers (2,093 LTs) in Brazil from 1988 to 2015. HCC-R with histologic confirmation was seen in 40 patients (14.4%). RESULTS: Most of them were male with cirrhosis secondary to viral hepatitis. Only 37.5% underwent chemoembolization, and 50% had cold ischemia time >8 hours. From the explant analysis, most of the patients were outside Milan criteria and 37.5% had microvascular invasion. The donors were mostly male, and the median intensive care unit time was >3 days. The Kaplan-Meier survival was lower according to alpha-fetoprotein (AFP) >200 ng/dL (P = .02), and older donors and more blood transfusions were risk factors for HCC-R death. CONCLUSION: AFP >200 ng/mL was associated with lower survival, and older donors and more blood transfusions were risk factors for death after HCC-R. A trend to lower survival was observed in patients who did not have chemoembolization and had cold ischemia times >8 hours.


Subject(s)
Carcinoma, Hepatocellular/pathology , Cold Ischemia/adverse effects , Liver Neoplasms/pathology , Liver Transplantation/adverse effects , Neoplasm Recurrence, Local/etiology , Adult , Aged , Blood Transfusion/statistics & numerical data , Brazil , Carcinoma, Hepatocellular/surgery , Embolization, Therapeutic , Female , Humans , Kaplan-Meier Estimate , Liver Cirrhosis/surgery , Liver Cirrhosis/virology , Liver Neoplasms/surgery , Male , Middle Aged , Retrospective Studies , Risk Factors , Tissue Donors , alpha-Fetoproteins/analysis
7.
Transplant Proc ; 49(4): 898-901, 2017 May.
Article in English | MEDLINE | ID: mdl-28457421

ABSTRACT

OBJECTIVE: There has been much research on hepatic ischemia and reperfusion by means of short or longer interruption of the portal triad. The aim of this work was to evaluate the mitochondrial respiratory activity and liver histology at 2 different times after the Pringle maneuver. METHODS: Twenty-eight male Wistar rats, weighing ∼308 g, with histologic and mitochondrial study: immediate ischemic group (IIG; 40 minutes; 9 animals) and late ischemic group (LIG; 28 days; 9 animals). The rats were anesthetized and underwent a U-incision in the abdomen. In a simulated operation, manipulation of the hepatic pedicle was performed (5 animals immediate [ISG] and 5 late [LSG]). The hepatic pedicle was clamped for 20 minutes of ischemia foloowed by 20 minutes of reperfusion. The animals were killed under anesthesia. RESULTS: Mitochondria when stimulated by adenosine diphosphate or carbonylcyanide p-trifluoromethoxyphenylhydrazone had a significant respiratory reduction (P < .001). The respiratory control ratio in the LIG was altered (P < .02) compared with IIG. In the resting state, there was no change in the velocity of respiration between ischemic groups. Histopathologic findings showed 55.5% sinusoidal dilatation in IIG and 66.6% in LIG; 77.7% ballooning in IIG and 55.5% in LIG; and 11.1% focal necrosis in both IIG and LIG. CONCLUSIONS: The oxidative phosphorylation system recovered with improvement in mitochondrial respiration; however, morphologic recovery was associated with the type and intensity of injury.


Subject(s)
Hemostasis, Surgical/adverse effects , Ischemia/pathology , Liver Diseases/pathology , Mitochondria, Liver/metabolism , Reperfusion Injury/pathology , Reperfusion/adverse effects , Animals , Hemostasis, Surgical/methods , Ischemia/etiology , Liver/pathology , Liver Circulation , Liver Diseases/etiology , Male , Mitochondria, Liver/drug effects , Portal System , Rats , Rats, Wistar , Reperfusion/methods , Reperfusion Injury/etiology , Time Factors
8.
Braz J Med Biol Res ; 50(1): e5540, 2017 Jan 09.
Article in English | MEDLINE | ID: mdl-28076451

ABSTRACT

Recurrent hepatitis C after orthotopic liver transplantation (OLT) is universal and can lead to graft failure and, consequently, reduced survival. Hepatitis C treatment can be used to prevent these detrimental outcomes. The aim of this study was to describe rates of hepatitis C recurrence and sustained virological response (SVR) to interferon-based treatment after OLT and its relationship to survival and progression of liver disease through retrospective analysis of medical records of 127 patients who underwent OLT due to cirrhosis or hepatocellular carcinoma secondary to chronic hepatitis C between January 2002 and December 2013. Fifty-six patients were diagnosed with recurrent disease, 42 started interferon-based therapy and 37 completed treatment. Demographic, treatment- and outcome-related variables were compared between SVR and non-responders (non-SVR). There was an overall 54.1% SVR rate with interferon-based therapies. SVR was associated with longer follow-up after treatment (median 66.5 vs 37 months for non-SVR, P=0.03) and after OLT (median 105 vs 72 months, P=0.074), and lower rates of disease progression (15 vs 64.7%, P=0.0028) and death (5 vs 35.3%, P=0.033). Regardless of the result of therapy (SVR or non-SVR), there was a significant difference between treated and untreated patients regarding the occurrence of death (P<0.001) and months of survival (P<0.001). Even with suboptimal interferon-based therapies (compared to the new direct-acting antivirals) there is a 54.1% SVR rate to treatment. SVR is associated with improved survival and reduced risks of clinical decompensation, loss of the liver graft and death.


Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/surgery , Hepatitis C, Chronic/drug therapy , Interferons/therapeutic use , Liver Cirrhosis/surgery , Liver Neoplasms/surgery , Liver Transplantation , Postoperative Complications/drug therapy , Adult , Aged , Carcinoma, Hepatocellular/etiology , Disease Progression , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/mortality , Humans , Liver Cirrhosis/etiology , Liver Neoplasms/etiology , Liver Transplantation/mortality , Male , Middle Aged , Recurrence , Retrospective Studies , Risk Factors , Survival Analysis , Sustained Virologic Response , Treatment Outcome
9.
Transplant Proc ; 48(7): 2375-2378, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27742301

ABSTRACT

BACKGROUND: Biliary complications are important causes of morbidity and mortality in patients undergoing hepatic surgery. The aim of the study was to evaluate late liver alterations after a long period of choledochal clamping in Wistar rats. METHODS: Ten male Wistar rats, weighing 304 grams, anesthetized with sodium thiopental (25 mg/kg) and xylazine (10 mg/kg) intravenously, were distributed into 2 groups: the choledochal clamping group (CCG) and the operation sham group (OSG), with 5 animals each submitted to an abdominal incision. In the CCG, the choledochal was isolated, dissected, and clamped with a microvascular clamp for 40 minutes. After this occlusion time, the clamp was removed and the incision was closed. In the OSG the animals, under normal conditions, were submitted only to anesthesia and laparotomy for choledochal manipulation. In all animals, after the 31st day, a hepatic biopsy was carried out for histology and blood biochemical tests: total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase. The animals were euthanized under anesthesia. This research was approved by the Ethics Committee on Animal Use (CEUA, Unicamp, No. 2511-1). RESULTS: In the CCG, 100% of the animals showed bile duct dilatation, ductular proliferation, and portal inflammatory infiltrate; 60% showed regenerative nodule formation; and 80% had porta-porta septa and foci of necrosis, all of which were not found in the OSG. All CCG group biochemical tests had significant increases (P < .05) compared with OSG. CONCLUSIONS: Long-time choledochal clamping in Wistar rats caused hepatic dysfunction and biochemical and histological injuries with degrees of distortion to the hepatic architecture.


Subject(s)
Bile Ducts/pathology , Bile Ducts/surgery , Cholestasis/complications , Liver Cirrhosis/etiology , Animals , Bilirubin , Constriction , Disease Models, Animal , Liver Function Tests , Male , Rats , Rats, Wistar
10.
Braz. j. med. biol. res ; 49(3): e4808, Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-771942

ABSTRACT

Biliary atresia (BA) is classically described at the neonatal age. However, rare cases of BA in older infants have also been reported. We report four cases of late-onset BA in infants older than 4 weeks (3 males, 1 female), and describe the diagnostic and management difficulties. One of the cases had a late-onset (29 weeks) presentation with a successful surgical procedure. We highlight the importance of this unusual differential diagnosis in infants with cholestatic syndrome, who may benefit from Kasai surgery, regardless of age.


Subject(s)
Humans , Male , Female , Infant , Biliary Atresia/diagnosis , Late Onset Disorders/diagnosis , Liver/pathology , Biliary Atresia/pathology , Biliary Atresia/surgery , Biopsy , Diagnosis, Differential , Hepatic Artery/pathology , Late Onset Disorders/pathology , Late Onset Disorders/surgery
11.
Braz J Med Biol Res ; 49(3)2016 Mar.
Article in English | MEDLINE | ID: mdl-26840713

ABSTRACT

Biliary atresia (BA) is classically described at the neonatal age. However, rare cases of BA in older infants have also been reported. We report four cases of late-onset BA in infants older than 4 weeks (3 males, 1 female), and describe the diagnostic and management difficulties. One of the cases had a late-onset (29 weeks) presentation with a successful surgical procedure. We highlight the importance of this unusual differential diagnosis in infants with cholestatic syndrome, who may benefit from Kasai surgery, regardless of age.


Subject(s)
Biliary Atresia/diagnosis , Late Onset Disorders/diagnosis , Liver/pathology , Biliary Atresia/pathology , Biliary Atresia/surgery , Biopsy , Diagnosis, Differential , Female , Hepatic Artery/pathology , Humans , Infant , Late Onset Disorders/pathology , Late Onset Disorders/surgery , Male
12.
Transplant Proc ; 47(4): 1038-41, 2015 May.
Article in English | MEDLINE | ID: mdl-26036513

ABSTRACT

BACKGROUND: Although the intermittent Pringle maneuver is used for major transplant surgery, traumas, and hepatic protection, long ischemia time and reperfusion may limit some protection in Wistar rats. The aim of the study was to evaluate the protection effects of intermittent clamping in the total hepatic pedicle after a long period of ischemia and reperfusion in Wistar rats. METHODS: Forty-two male Wistar rats, weighing ± 327.7 g, were anesthetized intravenously with sodium thiopental and given a U-shaped incision in the abdomen. The total hepatic pedicle was isolated and subjected to clamping with a microvascular clamp. Groups included were the continuous group (CG, n = 14, 40 minutes of ischemia/40 minutes of reperfusion); the intermittent group (IG, n = 14, 4 cycles a 10 minute ischemia/reperfusion 10 minutes); and the sham group (SG, n = 14, 80 minutes of observation time). Blood collection for transaminase dosage was carried out, and hepatic biopsy specimens were taken for mitochondrial respiration and histological evaluation. RESULTS: In groups CG and IG, aspartate aminotransferase and alanine aminotransferase enzymes were elevated in comparison to group SG (P < .008); mitochondrias, when stimulated by use of adenosine diphosphate or carbonylcyanide p-trifluoromethoxyphenylhydrazone, had a significant decrease in mitochondrial respiration (P < .05), and the respiratory control ratio in the ischemic groups was lower (P < .03) when compared with the GS. On histological examination, 100% of the GC had lesions: 33% focal hemorrhagic necrosis, 17% sinuzoidal congestion and/or vacuolization, and 50% venous congestion; in the IG, 100% had lesions: 43% sinusoidal congestion and/or vacuolization and 57% venous congestion. CONCLUSIONS: The intermittent total hepatic pedicle clamping for a long period of time in the Wistar rats had no efficacy in protection of liver injury.


Subject(s)
Cold Ischemia/methods , Liver Circulation/physiology , Liver Transplantation/adverse effects , Liver/blood supply , Reperfusion Injury/prevention & control , Animals , Disease Models, Animal , Liver/pathology , Male , Rats , Rats, Wistar
13.
Transplant Proc ; 46(6): 1875-8, 2014.
Article in English | MEDLINE | ID: mdl-25131058

ABSTRACT

INTRODUCTION: The temporary vascular occlusion of hepatic flow is one of the essential procedures in hepatic surgery. AIM: Evaluate the late liver alterations after intermittent pedicle hepatic clamping (IHPC) in Wistar rats. METHODS: Male Wistar rats (n = 14) with average weight of 281.1 g, were anesthetized with intraperitoneal ketamine 5%. The IHPC group (n = 7) was submitted to U-shaped abdominal incision; the hepatic pedicle was isolated and submitted to IHPC ischemia 4 times, 5 minutes each, followed by reperfusion 4 times, 5 minutes each. The simulated operation group (n = 7) was subjected to anesthesia, laparotomy, and manipulation of the hepatic pedicle. On day 35, after fasting for 12 hours, liver biopsies were collected and blood was tested for liver aminotransferases (aspartate aminotransferase/alanine aminotransferase). RESULTS: All the IHPC group animals had a dilated common bile duct and increased liver enzymes (P < .05 by Mann-Whitney test). Ductular proliferation (100% of cases), porta-porta septa (42.8%), formation of lumps (42.8%), foci of necrosis (14.2%), and bile plugs (14, 2%) were observed only in the IHPC group. CONCLUSION: In rats, IHPC caused morphologic features leading to biliary obstruction.


Subject(s)
Cholestasis/etiology , Ischemia/pathology , Liver/blood supply , Reperfusion Injury/pathology , Animals , Common Bile Duct/pathology , Constriction , Dilatation, Pathologic , Liver Circulation , Male , Rats, Wistar , Reperfusion Injury/physiopathology
14.
Transplant Proc ; 46(7): 2433-6, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24998304

ABSTRACT

BACKGROUND: This article reports a case of hepar lobatum, a peculiar and rare type of liver deformity, originally described in association with infectious or parasitic diseases and with malignancies. CASE REPORT: We have described a 42-year-old woman with this disorder, which was unrelated to the known conditions and referred for liver transplantation for having clinical manifestations of cirrhosis, portal hypertension, and impaired hepatic function. CONCLUSIONS: The observed histologic pattern suggests that hepar lobatum could be, in some patients, the effect of a primary process of hamartomatous origin involving the organ vascular supply.


Subject(s)
Hypertension, Portal/surgery , Liver Transplantation , Liver/pathology , Adult , Diagnosis, Differential , Female , Humans , Hypertension, Portal/etiology , Liver Cirrhosis/congenital , Liver Cirrhosis/diagnosis
15.
Transplant Proc ; 45(5): 1907-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23769069

ABSTRACT

Hepatoportal sclerosis (HPS), first reported by Mikkelsen et al in 1965, is a pathologic condition that does not cause cirrhotic portal hypertension. The primary hepatic lesion in HPS is found in portal vein branches with preserved synthetic function. Rarely do patients with HPS need liver transplantation. The aim of this study was to describe the clinical and pathologic features of 6 HPS cases who underwent liver transplantation (OLT). From 2000 to 2008, 6 OLT candidates were diagnosed with HPS: 3 displayed bleeding varices and 4 ascites. Child-Pugh evaluation was class B (n = 4) or C (n = 2). The Model for End-stage Liver Disease scores were 18 (n = 2), 20 (n = 3), and 22 (n = 1). Cirrhosis resulted from presumed diagnoses of alcohol n = (1), autoimmune n = (2) or cryptogenic cirrhosis n = (3). On histologic examination, there was marked phlebosclerosis in all cases, including nonocclusive portal vein thrombosis (n = 3), intense portal fibrosis (n = 1), moderate portal fibrosis (n = 5), and uniform moderate sinusoidal dilatation without megasinusoid formation, but with ductal biliary proliferation and ductal biliary fibrosis in all cases. Cholestasis was observed in 1 and incomplete septal cirrhosis in 4 cases. None of the subjects showed histological features of the presumed underlying liver disease. The overall survival of this group was no different from that of other OLT patients. HPS causing hepatic failure may require liver transplantation. Fhlebosclerosis andportal fibrosis may contribute to the loss of hepatic synthesis leading to the need for hepatic transplant. Significant portal fibrosis and phlebosclerosis can contribute to hepatic parenchymal and posterior synthetic loss.


Subject(s)
Liver Failure/surgery , Liver Transplantation , Portal Vein/surgery , Sclerosis/surgery , Adult , Female , Humans , Liver Failure/complications , Male , Middle Aged , Sclerosis/complications
16.
Transplant Proc ; 45(3): 1157-9, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23622649

ABSTRACT

INTRODUCTION: Biliary complications after liver procedures can lead to morbidity and poor survival. AIM: The aim of this study was to evaluate the hepatic function after quick clamping of the common bile duct (BD) in Wistar rats. METHODS: Twelve male Wistar rats with a mean weight of 323.14 g were anesthetized with sodium thiopental intravenous (IV). The common BD Clamping Group (BDCG; n = 6) was submitted to an abdominal incision (2 cm); the BD was isolated, dissected, and underwent clamping for 10 minutes with a microvascular clamp. After this time, the clamp was removed and the incision closed. The Sham Operation Group (SOG; n = 6 rats), under normal conditions, were subjected only to anesthesia and laparotomy and later control tests. On the 28th day liver and choledoch biopsy and biochemical tests were performed on all animals: total bilirubin (TB), alkaline phosphatase (ALK-P), aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), and gamma-glutamyl transferase (GGT). After the tests all the rats were humanely killed while still under anesthesia. RESULTS: In this study 83% of the animals in the BDCG had large dilatation of the common BD with ductular proliferation, formation of septae, as well as multiple foci of parenchymal necrosis including micro-abscess formation. We also observed alterations in biochemical tests (P < .05). CONCLUSION: Our study demonstrated that BD clamping even for a short time was sufficient to generate important morphological alterations in the liver and BD, as confirmed by enzymatic and histological analysis. Therefore, this technique can be used as a model of biliary obstruction for future studies.


Subject(s)
Cholestasis , Animals , Male , Prospective Studies , Rats , Rats, Wistar
17.
Transplant Proc ; 44(8): 2438-40, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23026614

ABSTRACT

BACKGROUND: Liver transplantation is a controversial issue in the initial management of hepatocellular carcinoma (HCC). The aim of this study was to demonstrate that up-to-seven could be useful as a model in evaluating potential candidates for liver transplantation for HCC. METHODS: Between January 1997 and December 2010, 84 patients undergoing liver transplantation were analyzed for HCC. Pathologic variables included the number of lesions, maximal tumor diameter, vascular invasion, and tumor grade. The following variables were recorded: Age, gender, recurrence of HCC, survival, donor age, incidental, Milan criteria, Model for End-Stage Liver Disease score, and alpha-fetoprotein (AFP) levels. To evaluate variables we used the Kaplan-Meier method, Cox regression and Kolmogorov-Smirnov test. RESULTS: There were 68 (80.9%) patients within up-to-seven criteria and 16 (19.1%) beyond this criteria. AFP levels were 96.4 versus 464.3 ng/dL in patients within versus beyond up-to-seven criteria. The median diameter of the largest nodule was 22.2 versus 32.0 mm in patients within versus beyond up-to-seven criteria, respectively. The median sum of nodules was 1.8 and 5.6 nodules in patients within versus beyond up-to-seven criteria. Vascular invasion was present in 11 (13.0%) patients within versus 7 (8.3%) beyond. Recurrence was observed in 9 (10.7%) patients and only 3 were beyond up-to-seven criteria, 2 had vascular invasion, and another showed poor differentiation. Post liver transplantation survival rates were 87.7%, 74.5%, and 65.3% at 1, 3, and 5 years in patients within up-to-seven versus 80.7%, 51.7%, and 32.1% beyond (P = .03). Similar results were observed when we applied Milan criteria or expanded Milan criteria. The largest nodule was the only predictive factor after proportional hazard Cox regression application (Beta = 0.037; exponent = 1.0377; Wald = 4.542; P = .03). In the present study, up-to-seven criteria could be useful to evaluate potential liver transplant candidates due to HCC.


Subject(s)
Carcinoma, Hepatocellular/surgery , Decision Support Techniques , Liver Neoplasms/surgery , Liver Transplantation/adverse effects , Adult , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Transplantation/mortality , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Proportional Hazards Models , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Tumor Burden , Young Adult , alpha-Fetoproteins/analysis
18.
Transplant Proc ; 43(4): 1362-4, 2011 May.
Article in English | MEDLINE | ID: mdl-21620130

ABSTRACT

INTRODUCTION: Orthotopic liver transplantation (OLT) is a rational therapeutic option for early-stage hepatocellular carcinoma (HCC) providing a potential cure and improving survival. METHODS: This retrospective study of a longitudinal cohort used an electronic database collected prospectively from September 1997 to May 2010. The variables were gender, age (years), and alpha-fetoprotein (AFP) level (ng/mL). In explanted livers we observed: microvascular or macrovascular invasion, number of nodules and their largest size, Edmondson-Steiner histological differentiation, incidental tumor transarterial chemoembolization (TACE), Milan criteria, and previous down-staging. RESULTS: Five of 83 (6.0%) subjects including 68 (82%) males with a mean time to diagnosis of 9 months experienced tumor relapses. Mean patient age at HCC recurrence was 55.3 years for male and 44.6 years for female subjects. Vascular invasion was detected in 17/83 (20.5%) subjects, namely 2% of macrovascular invasion, and 52.5% with expanded Milan criteria due to an increased number and size of nodules in the explanted livers. An incidental tumor was observed in 29.5% of cases. Preoperative TACE treatment was performed in 13 (15.6%) patients. None of the patients who had a HCC recurrence had undergone TACE. AFP level at the time of recurrence was around 1,900 ng/mL. The predictive factor for mortality was nodule size (P=.04; hazard ratio=0.0269; confidence interval [CI], 95% 0.0094-0.299). CONCLUSION: Patients with relapses showed the worst survival and tumor size was a predictive factor for recurrence.


Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Liver Transplantation/adverse effects , Adolescent , Adult , Aged , Brazil , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Transplantation/mortality , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Proportional Hazards Models , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , Survival Rate , Time Factors , Treatment Outcome , Tumor Burden , Young Adult
19.
Transplant Proc ; 42(10): 4116-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21168640

ABSTRACT

Budd-Chiari syndrome (BCS) in patients progressing to cirrhosis is an indication for liver transplantation. At this stage of disease, it is common to find large benign hepatocellular nodules (LBHNs) of undetermined cause that may be confused with hepatocellular carcinoma (HCC). Patients with indications for liver transplantation are currently classified according to the MELD (Model for End-Stage Liver Disease) severity score. When they fit Barcelona and Milan eligibility criteria for HCC, they receive 20 points. Thus, misdiagnosis of HCC leads to a privileged position on the waiting list. Herein, we have reported three BCS cases of cirrhotic patients who underwent liver transplantation; the pathologic results of their explanted livers showed LBHN. We analyzed three of 489 OLT who had chronic venous outflow obstruction (CVOO) the first case: was a 19-year-old man, with BCS of undetermined cause. The second 20-year-old female patients displayed BCS due to antiphospholipid syndrome the third, 45-year-old man had CVOO diagnosed preliminarily due to cryptogenic cirrhosis in the explanted liver. In the three cases, the nodules in the explant measured 0.5 to 2.4 cm. In the first case, the diagnosis was not in doubt; in the second case, 23 nodules were confused with HCC histologic evaluation, and in the third case three larger hypervascular nodules were misdiagnosed as HCC in the preoperative period despite low alpha-fetoprotein levels. In conclusion it is fundamental to recognize these benign lesions so as to avoid misdiagnosis, thereby allowing the proper selection of candidates for liver transplantation.


Subject(s)
Budd-Chiari Syndrome/diagnosis , Carcinoma, Hepatocellular/diagnosis , Liver Cirrhosis/complications , Liver Neoplasms/diagnosis , Adult , Budd-Chiari Syndrome/complications , Budd-Chiari Syndrome/physiopathology , Budd-Chiari Syndrome/surgery , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/physiopathology , Diagnosis, Differential , Female , Humans , Liver Cirrhosis/physiopathology , Liver Cirrhosis/surgery , Liver Neoplasms/complications , Liver Neoplasms/physiopathology , Liver Transplantation , Male , Middle Aged , Waiting Lists
20.
Transplant Proc ; 42(10): 4184-6, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21168659

ABSTRACT

INTRODUCTION: Influenza is a common cause of respiratory infection in transplant recipients. It is expected that A/H1N1 influenza virus causes more severe disease in solid-organ recipients. Our goal was to describe two A/H1N1 infections that occurred after Orthotopic liver transplantation followed by acute allograft rejection episodes. CASE REPORTS: From March 2009 to March 2010 we observe two liver transplant patients with symptoms suggestive of A/H1N1 infection. The diagnosis was out based on a temperature of 37.8°C (100°F) or higher and the presence of a cough or using materials from anasopharyngeal and oropharyngeal swabs a sore throat. The diagnosis was confirmed by viral RNA detection by real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR) using materials from nasopharyngeal and oropharyngeal swabs. We performed the RT-PCR assay for A/H1N1 detection in a liver biopsy from one patient. Both patients were treated with usual doses of oseltamivir (75 mg twice daily for 5 days). One patient developed acute bacterial sinusitis requiring antibiotic therapy. Thereafter the liver enzymes increased and transplant biopsies showed moderate-to-severe acute cellular rejection. They were treated with corticosteroids. The liver enzymes normalized after 3 months. CONCLUSION: A/H1N1 influenza can lead to a severe acute cellular rejection episode with corticosteroid resistant treatment in liver transplant patients. Transplant centers should be aware of a possible relationship between A/H1N1 infections and acute allograft rejection episodes.


Subject(s)
Graft Rejection , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/physiopathology , Liver Transplantation , Adult , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human/virology , Male , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction
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