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Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular carcinoma via regulating Myd88 expression through H3K27 modification.

Fri, 10/13/2017 - 12:45

Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular carcinoma via regulating Myd88 expression through H3K27 modification.

Cell Death Dis. 2017 Oct 12;8(10):e3124

Authors: Xu X, Yin Y, Tang J, Xie Y, Han Z, Zhang X, Liu Q, Qin X, Huang X, Sun B

Abstract
Enhanced Myd88 expression has been found in various parenchymal tumors especially in hepatocellular carcinoma with little mechanism of its upregulation known. A lot of long non-coding RNAs are reported to regulate the protein-coding genes which have location association through various mechanisms. In our study we confirmed a new long non-coding RNA Myd88 aberrant upregulated in HCC located upstream of Myd88 and verified a positive regulation relationship between them indicating that Lnc-Myd88 might participate in the enhanced expression of Myd88 in HCC. The gain- and loss-of-function analysis revealed that Lnc-Myd88 could promote the proliferation and metastasis of HCC both in vitro and in vivo. In addition, ChIP assays demonstrated that Lnc-Myd88 might increase Myd88 expression through enhancing H3K27Ac in the promoter of Myd88 gene, thus resulting in the activation of both NF-κB and PI3K/AKT signal pathways. In conclusion, we proposed that Lnc-Myd88 might serve as a novel diagnosis and therapeutic target for HCC.

PMID: 29022910 [PubMed - in process]

Unique manifestations of biliary atresia provide new immunological insight into its etiopathogenesis.

Fri, 10/13/2017 - 12:45
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Unique manifestations of biliary atresia provide new immunological insight into its etiopathogenesis.

Pediatr Surg Int. 2017 Oct 11;:

Authors: Muraji T, Ohtani H, Ieiri S

Abstract
Biliary atresia (BA) is a unique cholestatic disease of newborns with a background of exaggerated immune response in the liver of unknown mechanism. Three hypotheses have been proposed; autoimmune type of cholangiopathy triggered by virus infection, graft-versus-host disease type of immune-mediated disease associated with maternal microchimerism and ductal plate malformation theory. Researchers on virus infection theory have experimentally explored immune process causing cholangiopathy on murine models of this disease, while in maternal microchimerism hypothesis were detected maternal cells in the BA patients' liver, of which roles are yet to be determined. Ductal plate malformation theory is an intriguing hypothesis in the sense that it suggests the onset of this disease is in the first trimester. This theory can be secondary to either one of these two immune-related insults. In this review, four unique points are focused; (1) the timing of onset, (2) hepatitis-like pathological picture, (3) heterogenous atrophy of the liver segments when advanced, and (4) swollen lymph nodes at the porta hepatis. These unique clinicopahtological aspects of this disease should be well explained by these hypotheses.

PMID: 29022092 [PubMed - as supplied by publisher]

Early small bowel perforation due to aflibercept.

Fri, 10/13/2017 - 12:45
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Early small bowel perforation due to aflibercept.

Drug Discov Ther. 2017 Oct 11;:

Authors: Moussallem T, Lim C, Osseis M, Esposito F, Lahat E, Fuentes L, Salloum C, Azoulay D

Abstract
In patients with malignancy who receive aflibercept based chemotherapy, gastrointestinal perforation is among the reported adverse events with a prevalence of 1.9%. This complication may lead to mortality up to 10.8%. We here report a case of small bowel perforation that occurred fifteen days after the first cycle of aflibercept in a 58-year old female who had metachronous colorectal liver metastases. Emergency laparotomy was performed and revealed a small bowel perforation without any anastomotic dehiscence. Surgery was followed by uneventful outcome. The use of aflibercept in patients with malignancy may be associated with very early gastrointestinal perforation and this should be known by oncologist and surgeons.

PMID: 29021501 [PubMed - as supplied by publisher]

Nanoparticle-mediated radiopharmaceutical-excited fluorescence molecular imaging allows precise image-guided tumor-removal surgery.

Fri, 10/13/2017 - 12:45
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Nanoparticle-mediated radiopharmaceutical-excited fluorescence molecular imaging allows precise image-guided tumor-removal surgery.

Nanomedicine. 2017 May;13(4):1323-1331

Authors: Hu Z, Chi C, Liu M, Guo H, Zhang Z, Zeng C, Ye J, Wang J, Tian J, Yang W, Xu W

Abstract
Fluorescent molecular imaging technique has been actively explored for optical image-guided cancer surgery in pre-clinical and clinical research and has attracted many attentions. However, the efficacy of the fluorescent image-guided cancer surgery can be compromised by the low signal-to-noise ratio caused by the external light excitation. This study presents a novel nanoparticle-mediated radiopharmaceutical-excited fluorescent (REF) image-guided cancer surgery strategy, which employs the internal dual-excitation of europium oxide nanoparticles through both gamma rays and Cerenkov luminescence emitted from radiopharmaceuticals. The performance of the novel image-guided surgery technique was systematically evaluated using subcutaneous breast cancer 4 T1 tumor models, orthotropic and orthotropic-ectopic hepatocellular carcinoma tumor-bearing mice. The results reveal that the novel REF image-guided cancer surgery technique exhibits high performance of detecting invisible ultra-small size tumor (even less than 1 mm) and residual tumor tissue. Our study demonstrates the high potential of the novel image-guided cancer surgery for precise tumor resection.

PMID: 28115248 [PubMed - indexed for MEDLINE]

Use of the levonorgestrel 52-mg intrauterine system in adolescent and young adult solid organ transplant recipients: a case series.

Fri, 10/13/2017 - 12:45
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Use of the levonorgestrel 52-mg intrauterine system in adolescent and young adult solid organ transplant recipients: a case series.

Contraception. 2017 Apr;95(4):378-381

Authors: Huguelet PS, Sheehan C, Spitzer RF, Scott S

Abstract
This case series reports on the safety and efficacy of the levonorgestrel 52-mg intrauterine system in adolescent and young adult solid organ transplant recipients. All patients used the device for contraception, with no documented cases of disseminated pelvic infection or unplanned pregnancy.

PMID: 27940059 [PubMed - indexed for MEDLINE]

High serum soluble CD40L levels previously to liver transplantation in patients with hepatocellular carcinoma are associated with mortality at one year.

Thu, 10/12/2017 - 10:01

High serum soluble CD40L levels previously to liver transplantation in patients with hepatocellular carcinoma are associated with mortality at one year.

J Crit Care. 2017 Sep 18;43:316-320

Authors: Lorente L, Rodriguez ST, Sanz P, Pérez-Cejas A, Padilla J, Díaz D, González A, Martín MM, Jiménez A, Barrera MA

Abstract
PURPOSE: CD40L and its soluble form (sCD40L) are proteins of the tumor necrosis factor superfamily (TNFSF) that exhibit prothrombotic and proinflammatory properties when binding to CD40, which is a cell surface receptor of the tumor necrosis factor receptor superfamily (TNFRSF). High circulating levels of sCD40L have been associated with poor prognosis in patients with hepatocellular carcinoma (HCC). However, it is unknown whether there is an association between circulating sCD40L levels and survival in patients with HCC underwent to liver transplantation (LT), and this was the objective of that study.
METHODS: Serum sCD40L levels were measured in a total of 139 patients before LT (124 survivors at 1year of LT and 15 non-survivors). The end-point study was 1year survival after liver LT.
RESULTS: We found that 1-year non-surviving patients showed higher serum sCD40L levels than survivor patients (p=0.02). We found in logistic regression analysis that serum sCD40L levels higher than 321pg/mL (Odds Ratio=6.86; 95% confidence interval=2.06-22.76; p=0.002) and age of LT deceased donor were associated with death at 1year.
CONCLUSIONS: The new finding of our study was that high serum sCD40L levels previously to LT in patients with HCC are associated with higher mortality at one year.

PMID: 29020665 [PubMed - as supplied by publisher]

Relationship between viremia and specific organ damage in Ebola patients: a cohort study.

Thu, 10/12/2017 - 10:01

Relationship between viremia and specific organ damage in Ebola patients: a cohort study.

Clin Infect Dis. 2017 Aug 20;:

Authors: Lanini S, Portella G, Vairo F, Kobinger GP, Pesenti A, Langer M, Kabia S, Brogiato G, Amone J, Castilletti C, Miccio R, Capobianchi MR, Strada G, Zumla A, Di Caro A, Ippolito G, INMI-EMERGENCY EBOV Sierra Leone Study group

Abstract
Background: Pathogenesis of Ebola virus disease remains poorly understood. We used concomitant determination of routine laboratory biomarkers and Ebola viremia to explore the potential role of viral replication in specific organ damage.
Methods: We recruited patients with detectable Ebola viremia admitted to the EMERGENCY ONG ONLUS Ebola Treatment Center in Sierra Leone. Repeated measure of Ebola viremia, ALT, AST, bilirubin, CPK, LDH, aPTT, INR, creatinine and BUN were recorded. Patients were followed-up since admission until death or discharge.
Results: One hundred patients (49 survivors and 51 non-survivors) were included in the analysis. Unadjusted analysis to compare survivors and non-survivors provided evidence that all biomarkers were significantly above the normal range and that the extent of these abnormalities was generally higher in non-survivors than in survivors. Multivariable mixed effect models provided strong evidence for a biological gradient (suggestive of a direct role in organ damage) between the viremia levels and either ALT, AST, CPK LDH, aPTT and INR. In contrast no direct linear association was found between viremia and either creatinine, BUN or bilirubin.
Conclusion: This study provides evidence to support that Ebola virus may have a direct role in muscular damage and imbalance of the coagulation system. We did not found strong evidence suggestive of a direct role of Ebola virus in kidney damage. The role of the virus in liver damage remains unclear, but our evidence suggests that acute severe liver injury is not a typical feature of Ebola virus disease.

PMID: 29020340 [PubMed - as supplied by publisher]

Role of secondary prophylaxis with valganciclovir in the prevention of recurrent cytomegalovirus disease in solid organ transplant recipients.

Thu, 10/12/2017 - 10:01

Role of secondary prophylaxis with valganciclovir in the prevention of recurrent cytomegalovirus disease in solid organ transplant recipients.

Clin Infect Dis. 2017 Aug 07;:

Authors: Gardiner BJ, Chow JK, Price LL, Nierenberg NE, Kent DM, Snydman DR

Abstract
Background: Cytomegalovirus (CMV) is a major contributor to morbidity and mortality in solid organ transplant recipients (SOTR). Ganciclovir and valganciclovir are highly effective antiviral drugs whose role in primary prophylaxis and treatment of CMV disease is well established. The objective of this study was to examine the effect of secondary prophylaxis (SP) on the risk of relapse in SOTR following an episode of CMV disease.
Methods: We performed a retrospective cohort study of SOTR from 1995-2015 and used propensity score based inverse probability of treatment weighting methodology to control for confounding by indication. A weighted Cox model was created to determine the effect of SP on time to relapse within 1 year of treatment completion.
Results: Fifty-two heart, 34 liver, 79 kidney and 5 liver-kidney transplant recipients who completed treatment for an episode of CMV infection/disease were included. One hundred and twenty (70.6%) received SP (median duration 61 days, range 5- 365) and 39 (23%) relapsed. SP was protective against relapse from 0-6 weeks following treatment completion (HR 0.19, 95% CI 0.05-0.69) but after 6 weeks risk of relapse did not significantly differ between the two groups (HR 1.18, 95% CI 0.46-2.99).
Conclusions: Our findings demonstrate that use of SP following treatment of CMV disease did not confer long-term protection against relapse, although it did delay relapse while patients were receiving antivirals. This suggests that SP has limited clinical utility in the overall prevention of recurrent CMV disease.

PMID: 29020220 [PubMed - as supplied by publisher]

Change of sleep quality from pre- to 3 years post-solid organ transplantation: The Swiss Transplant Cohort Study.

Thu, 10/12/2017 - 10:01

Change of sleep quality from pre- to 3 years post-solid organ transplantation: The Swiss Transplant Cohort Study.

PLoS One. 2017;12(10):e0185036

Authors: Burkhalter H, Denhaerynck K, Huynh-Do U, Binet I, Hadaya K, De Geest S, Psychosocial Interest Group, Swiss Transplant Cohort Study

Abstract
BACKGROUND: Poor sleep quality (SQ) is common after solid organ transplantation; however, very little is known about its natural history. We assessed the changes in SQ from pre- to 3 years post-transplant in adult heart, kidney, liver and lung recipients included in the prospective nation-wide Swiss Transplant Cohort Study. We explored associations with selected variables in patients suffering persistent poor SQ compared to those with good or variable SQ.
METHODS: Adult single organ transplant recipients enrolled in the Swiss Transplant Cohort Study with pre-transplant and at least 3 post-transplant SQ assessment data were included. SQ was self-reported pre-transplant (at listing), then at 6, 12, 24 and 36 months post-transplant. A single SQ item was used to identify poor (0-5) and good sleepers (6-10). Between organ groups, SQ was compared via logistic regression analysis with generalized estimating equations. Within the group reporting persistently poor SQ, we used logistic regression or Kaplan-Meier analysis as appropriate to check for differences in global quality of life and survival.
RESULTS: In a sample of 1173 transplant patients (age: 52.1±13.2 years; 65% males; 66% kidney, 17% liver, 10% lung, 7% heart) transplanted between 2008 and 2012, pre- transplant poor SQ was highest in liver (50%) and heart (49%) recipients. Overall, poor SQ decreased significantly from pre-transplant (38%) to 24 months post-transplant (26%) and remained stable at 3 years (29%). Patients reporting persistently poor SQ had significantly more depressive symptomatology and lower global quality of life.
CONCLUSION: Because self-reported poor SQ is related to poorer global quality of life, these results emphasize the need for further studies to find suitable treatment options for poor SQ in transplant recipients.

PMID: 29020112 [PubMed - in process]

The Best Choice for Second-Line Treatment in Standard Treatment-Refractory Children with Autoimmune Hepatitis.

Thu, 10/12/2017 - 10:01

The Best Choice for Second-Line Treatment in Standard Treatment-Refractory Children with Autoimmune Hepatitis.

J Pediatr Gastroenterol Nutr. 2017 Oct 10;:

Authors: Nastasio S, Sciveres M, Maggiore G

PMID: 29019854 [PubMed - as supplied by publisher]

Contemporary Policies Regarding Alcohol and Marijuana use Among Liver Transplant Programs in the United States.

Thu, 10/12/2017 - 10:01

Contemporary Policies Regarding Alcohol and Marijuana use Among Liver Transplant Programs in the United States.

Transplantation. 2017 Oct 10;:

Authors: Zhu J, Chen PY, Frankel M, Selby RR, Fong TL

Abstract
BACKGROUND: Alcoholic liver disease is a common indication for liver transplantation (OLT). Although OLT has been shown to confer survival benefit to patients with acute alcoholic hepatitis (AAH), historically most programs require a 6-month abstinence period prior to OLT which excludes patients with AAH. Marijuana has become legal in more than half the states in the United States. This survey of liver transplant programs was conducted to evaluate current policies regarding alcohol, marijuana and methadone use.
METHODS: A questionnaire was distributed to 100 UNOS-approved liver transplant programs in North America that have performed at least 30 liver transplants/year in the last 5 years.
RESULTS: Forty-nine programs responded. Only 43% of programs required a specific period of abstinence prior to transplant for alcoholic liver disease and only 26% enforced 6-month abstinence policy. For patients with AAH, 71% programs waived the 6-month abstinence requirement and considered psychosocial factors such as family support, patient's motivation or commitment to rehabilitate. Few programs used validated instruments to assess risk of relapse in AAH patients. Fourteen percent of programs transplant patients actively using marijuana and an additional 28% of programs listed patients using marijuana provided they discontinue by the time of OLT. Active methadone users were accepted in 45% of programs.
CONCLUSIONS: Policies regarding alcohol use have become more flexible particularly toward patients with AAH. Marijuana use is also more accepted. Although policies regarding alcohol and marijuana have changed significantly in the last decade, they remain highly variable among programs.

PMID: 29019813 [PubMed - as supplied by publisher]

Rhesus Alloimunization Occurs After Rh Incompatible Liver Transplantation in Children.

Thu, 10/12/2017 - 10:01

Rhesus Alloimunization Occurs After Rh Incompatible Liver Transplantation in Children.

Transplantation. 2017 Oct 10;:

Authors: Bolia R, Shankar S, Herd L, Hardikar W

PMID: 29019811 [PubMed - as supplied by publisher]

Management of Patients who Receive an Organ Transplant Abroad and Return Home for Follow-up Care: Recommendations From the Declaration of Istanbul Custodian Group.

Thu, 10/12/2017 - 10:01

Management of Patients who Receive an Organ Transplant Abroad and Return Home for Follow-up Care: Recommendations From the Declaration of Istanbul Custodian Group.

Transplantation. 2017 Oct 11;:

Authors: Domínguez-Gil B, Danovitch G, Martin DE, López-Fraga M, Van Assche K, Morris ML, Lavee J, Erlich G, Fadhil R, Busic M, Rankin G, Al-Rukhaimi M, O Connell P, Chin J, Norman T, Massari P, Kamel R, Delmonico FL, Declaration of Istanbul Custodian Group working group on ethical travel for transplantation.

Abstract
Eradicating transplant tourism depends upon complex solutions that include efforts to progress towards self-sufficiency in transplantation. Meanwhile, professionals and authorities are faced with medical, legal, and ethical problems raised by patients who return home after receiving an organ transplant abroad, particularly when the organ has been obtained through illegitimate means. In 2016, the Declaration of Istanbul Custodian Group convened an international, multidisciplinary workshop in Madrid, Spain, to address these challenges and provide recommendations for the management of these patients, which are presented in this paper. The core recommendations are grounded in the belief that principles of transparency, traceability and continuity of care applied to patients who receive an organ domestically should also apply to patients who receive an organ abroad. Governments and professionals are urged to ensure that, upon return, patients are promptly referred to a transplant center for evaluation and care; not cover the costs of transplants resulting from organ or human trafficking; register standardized information at official registries on patients who travel for transplantation; promote international exchange of data for traceability; and develop a framework for the notification of identified or suspected cases of transnational transplant-related crimes by health professionals to law enforcement agencies.

PMID: 29019810 [PubMed - as supplied by publisher]

Atrial fibrillation and central nervous complications in liver transplanted hereditary transthyretin amyloidosis patients.

Thu, 10/12/2017 - 10:01

Atrial fibrillation and central nervous complications in liver transplanted hereditary transthyretin amyloidosis patients.

Transplantation. 2017 Oct 11;:

Authors: Wange N, Anan I, Ericzon BG, Pennlert J, Pilebro B, Suhr OB, Wixner J

Abstract
BACKGROUND: Central nervous system (CNS) complications are increasingly noted in liver transplanted (LTx) hereditary transthyretin amyloid (ATTRm) amyloidosis patients; this suggests that the increased survival allows for intracranial ATTRm formation from brain synthesised mutant TTR. However, atrial fibrillation (AF), a recognised risk factor for ischemic CNS complications, is also observed after LTx. The aim of the study was to investigate the occurrence of CNS complications and AF in LTx ATTRm amyloidosis patients.
METHODS: The medical records of all LTx ATTRm amyloidosis patients in the county of Västerbotten, Sweden were investigated for information on CNS complications, AF, anticoagulation (AC) therapy, hypertension, cardiac ischemic disease, hypertrophy, and neurological status.
RESULTS: Sixty-three patients that had survived for three years or longer after LTx were included in the analysis. Twenty-five patients had developed 1 or more CNS complications at a median of 21 years after onset of disease. AF was noted in 21 patients (median time to diagnosis 24 years). Cerebrovascular events (CVE) developed in 17 (median time to event 21 years). CVEs occurred significantly more often in patients with AF (P<0.002). AC therapy significantly reduced CVEs, including bleeding in patients with AF (P=0.04). Multivariate analysis identified AF as the only remaining regressor with a significant impact on CVE (HR 3.8; 95% CI 1.1 - 9.5; P= 0.029) CONCLUSIONS: AF is an important risk factor for CVE in LTx ATTRm amyloidosis patients, and AC therapy should be considered. However the increased bleeding risk with AC therapy in patients with intracranial amyloidosis should be acknowledged.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

PMID: 29019809 [PubMed - as supplied by publisher]

Pediatric Liver Transplant: Techniques and Complications.

Thu, 10/12/2017 - 10:01

Pediatric Liver Transplant: Techniques and Complications.

Radiographics. 2017 Oct;37(6):1612-1631

Authors: Horvat N, Marcelino ASZ, Horvat JV, Yamanari TR, Batista Araújo-Filho JA, Panizza P, Seda-Neto J, Antunes da Fonseca E, Carnevale FC, Mendes de Oliveira Cerri L, Chapchap P, Cerri GG

Abstract
Liver transplant is considered to be the last-resort treatment approach for pediatric patients with end-stage liver disease. Despite the remarkable advance in survival rates, liver transplant remains an intricate surgery with significant morbidity and mortality. Early diagnosis of complications is crucial for patient survival but is challenging given the lack of specificity in clinical presentation. Knowledge of the liver and vascular anatomy of the donor and the recipient or recipients before surgery is also important to avoid complications. In this framework, radiologists play a pivotal role on the multidisciplinary team in both pre- and postoperative scenarios by providing a road map to guide the surgery and by assisting in diagnosis of complications. The most common complications after liver transplant are (a) vascular, including the hepatic artery, portal vein, hepatic veins, and inferior vena cava; (b) biliary; (c) parenchymal; (d) perihepatic; and (e) neoplastic. The authors review surgical techniques, the role of each imaging modality, normal posttransplant imaging features, types of complications after liver transplant, and information required in the radiology report that is critical to patient care. They present an algorithm for an imaging approach for pediatric patients after liver transplant and describe key points that should be included in radiologic reports in the pre- and postoperative settings. Online supplemental material is available for this article. (©)RSNA, 2017.

PMID: 29019744 [PubMed - in process]

IMPACT OF OBESITY AND SURGICAL SKILLS IN LAPAROSCOPIC TOTALLY EXTRAPERITONEAL HERNIOPLASTY.

Thu, 10/12/2017 - 10:01

IMPACT OF OBESITY AND SURGICAL SKILLS IN LAPAROSCOPIC TOTALLY EXTRAPERITONEAL HERNIOPLASTY.

Arq Bras Cir Dig. 2017 Jul-Sep;30(3):169-172

Authors: Kato JM, Iuamoto LR, Suguita FY, Essu FF, Meyer A, Andraus W

Abstract
BACKGROUND: Laparoscopic totally extraperitoneal (TEP) hernia repair is a technically demanding procedure. Recent studies have identified BMI as an independent factor for technical difficulty in the learning period.
AIM: To analyze the effect of overweight and obesity on the technical difficulties of TEP.
METHOD: Prospective study on patients who underwent a symptomatic inguinal hernia by means of the TEP technique. Were analyzed gender, BMI, previous surgery, hernia type, operative time and complications. Technical difficulty was defined by operative time, major complications and recurrence. Patients were classified into four groups: 1) underweight, if less than 18,5 kg/m²; 2) normal range if BMI between 18,5 and 24,9 kg/m²; 3) overweight if BMI between 25-29,9 kg/m²; and 4) obese if BMI≥30 kg/m².
RESULTS: The cohort had a total of 190 patients, 185 men and 5 women. BMI values ranged from 16-36 kg/m² (average 26 kg/m²). Average operating time was 55.4 min in bilateral hernia (15-150) and 37.8 min in unilateral (13-150). Time of surgery was statistically correlated with increased BMI in the first 93 patients (p=0.049).
CONCLUSION: High BMI and prolonged operative time are undoubtedly correlated. However, this relationship may be statistically significant only in the learning period. Although several clinical features can influence surgical time, upon reaching an experienced level, surgeons appear to easily handle the challenges.

PMID: 29019555 [PubMed - in process]

Evaluation of the treatment of the hepatocarcinoma nodules in the patients in waiting list for liver transplant.

Thu, 10/12/2017 - 10:01

Evaluation of the treatment of the hepatocarcinoma nodules in the patients in waiting list for liver transplant.

Rev Col Bras Cir. 2017 Jul-Aug;44(4):360-366

Authors: Sá GPD, Carlotto JRM, Vicentine FPP, Romero L, Tejada DFP, Salzedas AA, Lopes GJ, Gonzalez AM

Abstract
OBJECTIVE: to compare the outcome of liver transplantation for hepatocarcinoma in submitted or not to locoregional treatment and downstaging regarding survival and risk of recurrence in transplant waiting list patients.
METHODS: retrospective study of patients with hepatocarcinoma undergoing liver transplantation in the metropolitan region of São Paulo, between January 2007 and December 2011, from a deceased donor. The sample consisted of 414 patients. Of these, 29 patients were included in the list by downstaging. The other 385 were submitted or not to locoregional treatment.
RESULTS: the analysis of 414 medical records showed a predominance of male patients (79.5%) with average age of 56 years. Treatment of the lesions was performed in 56.4% of patients on the waiting list for transplant. The most commonly used method was chemoembolization (79%). The locoregional patients undergoing treatment had a significant reduction in nodule size greater (p<0.001). There was no statistical difference between groups with and without locoregional treatment (p=0.744) and on mortality among patients enrolled in the Milan criteria or downstaging (p=0.494).
CONCLUSION: there was no difference in survival and recurrence rate associated with locoregional treatment. Patients included by downstaging process had comparable survival results to those previously classified as Milan/Brazil criteria.

PMID: 29019539 [PubMed - in process]

In Situ Liver Expression of HBsAg/CD3-Bispecific Antibodies for HBV Immunotherapy.

Thu, 10/12/2017 - 10:01

In Situ Liver Expression of HBsAg/CD3-Bispecific Antibodies for HBV Immunotherapy.

Mol Ther Methods Clin Dev. 2017 Dec 15;7:32-41

Authors: Kruse RL, Shum T, Legras X, Barzi M, Pankowicz FP, Gottschalk S, Bissig KD

Abstract
Current therapies against hepatitis B virus (HBV) do not reliably cure chronic infection, necessitating new therapeutic approaches. The T cell response can clear HBV during acute infection, and the adoptive transfer of antiviral T cells during bone marrow transplantation can cure patients of chronic HBV infection. To redirect T cells to HBV-infected hepatocytes, we delivered plasmids encoding bispecific antibodies directed against the viral surface antigen (HBsAg) and CD3, expressed on almost all T cells, directly into the liver using hydrodynamic tail vein injection. We found a significant reduction in HBV-driven reporter gene expression (184-fold) in a mouse model of acute infection, which was 30-fold lower than an antibody only recognizing HBsAg. While bispecific antibodies triggered, in part, antigen-independent T cell activation, antibody production within hepatocytes was non-cytotoxic. We next tested the bispecific antibodies in a different HBV mouse model, which closely mimics the transcriptional template for HBV, covalently closed circular DNA (cccDNA). We found that the antiviral effect was noncytopathic, mediating a 495-fold reduction in HBsAg levels at day 4. At day 33, bispecific antibody-treated mice exhibited 35-fold higher host HBsAg immunoglobulin G (IgG) antibody production versus untreated groups. Thus, gene therapy with HBsAg/CD3-bispecific antibodies represents a promising therapeutic strategy for patients with HBV.

PMID: 29018834 [PubMed]

A Case of Left Renal Vein Ligation in a Patient with Solitary Left Kidney Undergoing Liver Transplantation to Control Splenorenal Shunt and Improve Portal Venous Flow.

Thu, 10/12/2017 - 10:01

A Case of Left Renal Vein Ligation in a Patient with Solitary Left Kidney Undergoing Liver Transplantation to Control Splenorenal Shunt and Improve Portal Venous Flow.

Am J Case Rep. 2017 Oct 11;18:1086-1089

Authors: Martino RB, Júnior ER, Manuel V, Rocha-Santos V, D'Albuquerque LAC, Andraus W

Abstract
BACKGROUND Adequate portal venous flow is required for successful liver transplantation. Reduced venous flow and blood flow 'steal' by collateral vessels are a concern, and when there is a prominent splenorenal shunt present, ligation of the left renal vein has been recommended to improve portal venous blood flow. CASE REPORT A 51-year-old man who had undergone right nephrectomy in childhood required liver transplantation for liver cirrhosis and hepatocellular carcinoma due to hepatitis C virus (HCV) infection. The patient had no other comorbidity and no history of hepatorenal syndrome. At transplantation surgery, portal venous flow was poor and did not improve with ligation of shunt veins, but ligation of the left renal vein improved portal venous flow. On the first and fifth postoperative days, the patient was treated with basiliximab, a chimeric monoclonal antibody to the IL-2 receptor, and methylprednisolone. The calcineurin inhibitor, tacrolimus, was introduced on the fifth postoperative day. On the sixteenth postoperative day, renal color Doppler ultrasound showed normal left renal parenchyma; hepatic Doppler ultrasound showed good portal vein flow and preserved hepatic parenchyma in the liver transplant. CONCLUSIONS This case report has shown that in a patient with a single left kidney, left renal vein ligation is feasible and safe in a patient with no other risk factors for renal impairment following liver transplantation. Modification of postoperative immunosuppression to avoid calcineurin inhibitors in the very early postoperative phase may be important in promoting good recovery of renal function and to avoid the need for postoperative renal dialysis.

PMID: 29018183 [PubMed - in process]

Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver transplantation of human liver allografts from extended criteria donors (ECD) in donation after brain death (DBD): a prospective multicentre randomised controlled trial (HOPE ECD-DBD).

Thu, 10/12/2017 - 10:01

Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver transplantation of human liver allografts from extended criteria donors (ECD) in donation after brain death (DBD): a prospective multicentre randomised controlled trial (HOPE ECD-DBD).

BMJ Open. 2017 Oct 10;7(10):e017558

Authors: Czigany Z, Schöning W, Ulmer TF, Bednarsch J, Amygdalos I, Cramer T, Rogiers X, Popescu I, Botea F, Froněk J, Kroy D, Koch A, Tacke F, Trautwein C, Tolba RH, Hein M, Koek GH, Dejong CHC, Neumann UP, Lurje G

Abstract
INTRODUCTION: Orthotopic liver transplantation (OLT) has emerged as the mainstay of treatment for end-stage liver disease. In an attempt to improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with a higher incidence of primary graft non-function and/or delayed graft function. As such, several strategies have been developed aiming at reconditioning poor quality ECD liver allografts. Hypothermic oxygenated machine perfusion (HOPE) has been successfully tested in preclinical experiments and in few clinical series of donation after cardiac death OLT.
METHODS AND ANALYSIS: HOPE ECD-DBD is an investigator-initiated, open-label, phase-II, prospective multicentre randomised controlled trial on the effects of HOPE on ECD allografts in donation after brain death (DBD) OLT. Human whole organ liver grafts will be submitted to 1-2 hours of HOPE (n=23) via the portal vein before implantation and are going to be compared with a control group (n=23) of patients transplanted after conventional cold storage. Primary (peak and Δ peak alanine aminotransferase within 7 days) and secondary (aspartate aminotransferase, bilirubin and international normalised ratio, postoperative complications, early allograft dysfunction, duration of hospital and intensive care unit stay, 1-year patient and graft survival) endpoints will be analysed within a 12-month follow-up. Extent of ischaemia-reperfusion (I/R) injury will be assessed using liver tissue, perfusate, bile and serum samples taken during the perioperative phase of OLT.
ETHICS AND DISSEMINATION: The study was approved by the institutional review board of the RWTH Aachen University, Aachen, Germany (EK 049/17). The current paper represent the pre-results phase. First results are expected in 2018.
TRIAL REGISTRATION NUMBER: NCT03124641.

PMID: 29018070 [PubMed - in process]

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