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Young plasma reverses age-dependent alterations in hepatic function through the restoration of autophagy.

Thu, 12/07/2017 - 13:45
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Young plasma reverses age-dependent alterations in hepatic function through the restoration of autophagy.

Aging Cell. 2017 Dec 05;:

Authors: Liu A, Guo E, Yang J, Yang Y, Liu S, Jiang X, Hu Q, Dirsch O, Dahmen U, Zhang C, Gewirtz DA, Fang H

Abstract
Recent studies showing the therapeutic effect of young blood on aging-associated deterioration of organs point to young blood as the solution for clinical problems related to old age. Given that defective autophagy has been implicated in aging and aging-associated organ injuries, this study was designed to determine the effect of young blood on aging-induced alterations in hepatic function and underlying mechanisms, with a focus on autophagy. Aged rats (22 months) were treated with pooled plasma (1 ml, intravenously) collected from young (3 months) or aged rats three times per week for 4 weeks, and 3-methyladenine or wortmannin was used to inhibit young blood-induced autophagy. Aging was associated with elevated levels of alanine transaminase and aspartate aminotransferase, lipofuscin accumulation, steatosis, fibrosis, and defective liver regeneration after partial hepatectomy, which were significantly attenuated by young plasma injections. Young plasma could also restore aging-impaired autophagy activity. Inhibition of the young plasma-restored autophagic activity abrogated the beneficial effect of young plasma against hepatic injury with aging. In vitro, young serum could protect old hepatocytes from senescence, and the antisenescence effect of young serum was abrogated by 3-methyladenine, wortmannin, or small interfering RNA to autophagy-related protein 7. Collectively, our data indicate that young plasma could ameliorate age-dependent alterations in hepatic function partially via the restoration of autophagy.

PMID: 29210183 [PubMed - as supplied by publisher]

Kidney transplant outcomes from older deceased donors: A paired kidney analysis by the ERA-EDTA Registry.

Thu, 12/07/2017 - 13:45
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Kidney transplant outcomes from older deceased donors: A paired kidney analysis by the ERA-EDTA Registry.

Transpl Int. 2017 Dec 05;:

Authors: Pippias M, Jager KJ, Caskey F, Casula A, Erlandsson H, Finne P, Heaf J, Heinze G, Hoitsma A, Kramar R, Lempinen M, Magaz A, Midtvedt K, Mumford LL, Pascual J, Prütz KG, Sørensen SS, Traynor JP, Massy ZA, Ravanan R, Stel VS

Abstract
As the median age of deceased kidney donors rises, updated knowledge of transplant outcomes from older deceased donors in differing donor-recipient age groups is required. Using ERA-EDTA Registry data we determined survival outcomes of kidney allografts donated from the same older deceased donor (55-70 years), and transplanted into one recipient younger and one recipient of similar age to the donor. The recipient pairs were divided into two groups: group 1; younger (median age: 52 years) and older (60 years), and group 2; younger (41 years) and older (60 years). 1,410 adults were transplanted during 2000-2007. Compared to the older recipients the mean number of functioning graft years at 10-years was six months longer in the group 1 and group 2 younger recipients (p<0.001). Ten-year graft survival was 54% and 40% for the group 1 younger and older recipients, and 60% and 49% for the group 2 younger and older recipients. Paired Cox regression analyses showed a lower risk of graft failure (group 1 younger; adjusted relative risk [RRa]:0.57, 95%CI:0.41-0.79, and group 2 younger; RRa:0.63, 95%CI:0.47-0.85) in younger recipients. Outcomes from older deceased donor allografts transplanted into differing donor-recipient age groups are better than previously reported. These allografts remain a valuable transplant resource, particularly for similar-aged recipients. This article is protected by copyright. All rights reserved.

PMID: 29210108 [PubMed - as supplied by publisher]

Age-dependent cognitive dysfunction in untreated hereditary transthyretin amyloidosis.

Thu, 12/07/2017 - 13:45
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Age-dependent cognitive dysfunction in untreated hereditary transthyretin amyloidosis.

J Neurol. 2017 Dec 05;:

Authors: Martins da Silva A, Cavaco S, Fernandes J, Samões R, Alves C, Cardoso M, Kelly JW, Monteiro C, Coelho T

Abstract
Central nervous system (CNS) involvement in hereditary transthyretin (TTR) amyloidosis has been described in patients whose disease course was modified by liver transplant. However, cognitive dysfunction has yet to be investigated in those patients. Moreover, CNS involvement in untreated patients or asymptomatic mutation carriers remains to be studied. A series of 340 carriers of the TTRVal30Met mutation (180 symptomatic and 160 asymptomatic) underwent a neuropsychological assessment, which included the Dementia Rating Scale-2 (DRS-2), auditory verbal learning test, semantic fluency, phonemic fluency, and trail making test. Cognitive deficits were identified at the individual level, after adjusting the neuropsychological test scores for demographic characteristics (sex, age, and education), based on large national normative data. The presence of cognitive dysfunction was determined by deficit in DRS-2 and/or multiple cognitive domains. Participants were also screened for depression based on a self-report questionnaire. The frequency of cognitive dysfunction was higher (p = 0.003) in symptomatic (9%) than in asymptomatic (2%) carriers. Among older carriers (≥ 50 years), the frequency of cognitive dysfunction was higher (p < 0.001) in symptomatic (36%) than asymptomatic (4%) individuals. Among younger participants (< 50 years), the frequency of cognitive dysfunction was not different (p = 0.631) between symptomatic patients (2%) and asymptomatic (1%) carriers. This cross-sectional study shows that cognitive dysfunction is part of the broad spectrum of clinical manifestations in older hereditary TTR amyloidosis patients with peripheral polyneuropathy, even in the early stages of the disease.

PMID: 29209781 [PubMed - as supplied by publisher]

First case of cross-auxiliary double domino donor liver transplantation.

Thu, 12/07/2017 - 13:45
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First case of cross-auxiliary double domino donor liver transplantation.

World J Gastroenterol. 2017 Nov 28;23(44):7939-7944

Authors: Zhu ZJ, Wei L, Qu W, Sun LY, Liu Y, Zeng ZG, Zhang L, He EH, Zhang HM, Jia JD, Zhang ZT

Abstract
We report a case of double domino liver transplantation in a 32-year-old woman who was diagnosed with familial amyloid polyneuropathy (FAP) and liver dysfunction. A two-stage surgical plan was designed, and one domino graft was implanted during each stage. During the first stage, an auxiliary domino liver transplantation was conducted using a domino graft from a 4-year-old female child with Wilson's disease. After removing the right lobe of the FAP patient's liver, the graft was rotated 90 degrees counterclockwise and placed along the right side of the inferior vena cava (IVC). The orifices of the left, middle, and right hepatic veins were reconstructed using an iliac vein patch and then anastomosed to the right side of the IVC. Thirty days later, a second domino liver graft was implanted. The second domino graft was from a 3-year-old female child with an ornithine carbamyl enzyme defect, and it replaced the residual native liver (left lobe). To balance the function and blood flow between the two grafts, a percutaneous transcatheter selective portal vein embolization was performed, and "the left portal vein" of the first graft was blocked 9 mo after the second transplantation. The liver function indices, blood ammonia, and 24-h urinary copper levels were normal at the end of a 3-year follow-up. These two domino donor grafts from donors with different metabolic disorders restored normal liver function. Our experience demonstrated a new approach for resolving metabolic disorders with domino grafts and utilizing explanted livers from children.

PMID: 29209135 [PubMed - in process]

Short-term clinical outcomes of laparoscopic vs open rectal excision for rectal cancer: A systematic review and meta-analysis.

Thu, 12/07/2017 - 13:45
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Short-term clinical outcomes of laparoscopic vs open rectal excision for rectal cancer: A systematic review and meta-analysis.

World J Gastroenterol. 2017 Nov 28;23(44):7906-7916

Authors: Martínez-Pérez A, Carra MC, Brunetti F, de'Angelis N

Abstract
AIM: To review evidence on the short-term clinical outcomes of laparoscopic (LRR) vs open rectal resection (ORR) for rectal cancer.
METHODS: A systematic literature search was performed using Cochrane Central Register, MEDLINE, EMBASE, Scopus, OpenGrey and ClinicalTrials.gov register for randomized clinical trials (RCTs) comparing LRR vs ORR for rectal cancer and reporting short-term clinical outcomes. Articles published in English from January 1, 1995 to June, 30 2016 that met the selection criteria were retrieved and reviewed. The Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statements checklist for reporting a systematic review was followed. Random-effect models were used to estimate mean differences and risk ratios. The robustness and heterogeneity of the results were explored by performing sensitivity analyses. The pooled effect was considered significant when P < 0.05.
RESULTS: Overall, 14 RCTs were included. No differences were found in postoperative mortality (P = 0.19) and morbidity (P = 0.75) rates. The mean operative time was 36.67 min longer (95%CI: 27.22-46.11, P < 0.00001), the mean estimated blood loss was 88.80 ml lower (95%CI: -117.25 to -60.34, P < 0.00001), and the mean incision length was 11.17 cm smaller (95%CI: -13.88 to -8.47, P < 0.00001) for LRR than ORR. These results were confirmed by sensitivity analyses that focused on the four major RCTs. The mean length of hospital stay was 1.71 d shorter (95%CI: -2.84 to -0.58, P < 0.003) for LRR than ORR. Similarly, bowel recovery (i.e., day of the first bowel movement) was 0.68 d shorter (95%CI: -1.00 to -0.36, P < 0.00001) for LRR. The sensitivity analysis did not confirm a significant difference between LRR and ORR for these latter two parameters. The overall quality of the evidence was rated as high.
CONCLUSION: LRR is associated with lesser blood loss, smaller incision length, and longer operative times compared to ORR. No differences are observed for postoperative morbidity and mortality.

PMID: 29209132 [PubMed - in process]

Fatal gastrointestinal histoplasmosis 15 years after orthotopic liver transplantation.

Thu, 12/07/2017 - 13:45
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Fatal gastrointestinal histoplasmosis 15 years after orthotopic liver transplantation.

World J Gastroenterol. 2017 Nov 21;23(43):7807-7812

Authors: Agrawal N, Jones DE, Dyson JK, Hoare T, Melmore SA, Needham S, Thompson NP

Abstract
We report a case of ileo-colonic Histoplasmosis without apparent respiratory involvement in a patient who had previously undergone an orthotopic liver transplant (OLT) for primary biliary cholangitis 15 years earlier. The recipient lived in the United Kingdom, a non-endemic region for Histoplasmosis. However, she had previously lived in rural southern Africa prior to her OLT. The patient presented with iron deficiency anaemia, diarrhoea, abdominal pain and progressive weight loss. She reported no previous foreign travel, however, it later became known that following her OLT she had been on holiday to rural southern Africa. On investigation, a mild granulomatous colitis primarily affecting the right colon was identified, that initially improved with mesalazine. Her symptoms worsened after 18 mo with progressive ulceration of her distal small bowel and right colon. Mycobacterial, Yersinia, cytomegalovirus and human immunodeficiency virus infections were excluded and the patient was treated with prednisolone for a working diagnosis of Crohn's disease. Despite some early symptom improvement following steroids, there was subsequent deterioration with the patient developing gram-negative sepsis and multi-organ failure, leading to her death. Post-mortem examination revealed that her ileo-colonic inflammation was caused by Histoplasmosis.

PMID: 29209121 [PubMed - in process]

Laparoscopic VS open hepatectomy for hepatolithiasis: An updated systematic review and meta-analysis.

Thu, 12/07/2017 - 13:45
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Laparoscopic VS open hepatectomy for hepatolithiasis: An updated systematic review and meta-analysis.

World J Gastroenterol. 2017 Nov 21;23(43):7791-7806

Authors: Li H, Zheng J, Cai JY, Li SH, Zhang JB, Wang XM, Chen GH, Yang Y, Wang GS

Abstract
AIM: To perform a meta-analysis on laparoscopic hepatectomy VS conventional liver resection for treating hepatolithiasis.
METHODS: We conducted a systematic literature search on PubMed, Embase, Web of Science and Cochrane Library, and undertook a meta-analysis to compare the efficacy and safety of laparoscopic hepatectomy VS conventional open liver resection for local hepatolithiasis in the left or right lobe. Intraoperative and postoperative outcomes (time, estimated blood loss, blood transfusion rate, postoperative intestinal function recovery time, length of hospital stay, postoperative complication rate, initial residual stone, final residual stone and stone recurrence) were analyzed systematically.
RESULTS: A comprehensive literature search retrieved 16 publications with a total of 1329 cases. Meta-analysis of these studies showed that the laparoscopic approach for hepatolithiasis was associated with significantly less intraoperative estimated blood loss [weighted mean difference (WMD): 61.56, 95% confidence interval (CI): 14.91-108.20, P = 0.01], lower blood transfusion rate [odds ratio (OR): 0.41, 95%CI: 0.22-0.79, P = 0.008], shorter intestinal function recovery time (WMD: 0.98, 95%CI: 0.47-1.48, P = 0.01), lower total postoperative complication rate (OR: 0.52, 95%CI: 0.39-0.70, P < 0.0001) and shorter stay in hospital (WMD: 3.32, 95%CI: 2.32-4.32, P < 0.00001). In addition, our results showed no significant differences between the two groups in operative time (WMD: 21.49, 95%CI: 0.27-43.24, P = 0.05), residual stones (OR: 0.79, 95%CI: 0.50-1.25, P = 0.31) and stone recurrence (OR: 0.34, 95%CI: 0.11-1.08, P = 0.07). Furthermore, with subgroups analysis, our results proved that the laparoscopic approach for hepatolithiasis in the left lateral lobe and left side could achieve satisfactory therapeutic effects.
CONCLUSION: The laparoscopic approach is safe and effective, with less intraoperative estimated blood loss, fewer postoperative complications, reduced length of hospital stay and shorter intestinal function recovery time than with conventional approaches.

PMID: 29209120 [PubMed - in process]

Combined endovascular brachytherapy, sorafenib, and transarterial chemobolization therapy for hepatocellular carcinoma patients with portal vein tumor thrombus.

Thu, 12/07/2017 - 13:45
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Combined endovascular brachytherapy, sorafenib, and transarterial chemobolization therapy for hepatocellular carcinoma patients with portal vein tumor thrombus.

World J Gastroenterol. 2017 Nov 21;23(43):7735-7745

Authors: Zhang ZH, Liu QX, Zhang W, Ma JQ, Wang JH, Luo JJ, Liu LX, Yan ZP

Abstract
AIM: To evaluate the safety and efficacy of combined endovascular brachytherapy (EVBT), transarterial chemoembolization (TACE), and sorafenib to treat hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT).
METHODS: This single-center retrospective study involved 68 patients with unresectable HCC or those who were unfit for liver transplantation and percutaneous frequency ablation according to the BCLC classification. All patients had Child-Pugh classification grade A or B, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and MPVTT. The patients received either EVBT with stent placement, TACE, and sorafenib (group A, n = 37), or TACE with sorafenib (group B, n = 31). The time to progression (TTP) and overall survival (OS) were evaluated by propensity score analysis.
RESULTS: In the entire cohort, the 6-, 12-, and 24-mo survival rates were 88.9%, 54.3%, and 14.1% in group A, and 45.8%, 0%, and 0% in group B, respectively (P < 0.001). The median TTP and OS were significantly longer in group A than group B (TTP: 9.0 mo vs 3.4 mo, P < 0.001; OS: 12.3 mo vs 5.2 mo, P < 0.001). In the propensity score-matched cohort, the median OS was longer in group A than in group B (10.3 mo vs 6.0 mo, P < 0.001). Similarly, the median TTP was longer in group A than in group B (9.0 mo vs 3.4 mo, P < 0.001). Multivariate Cox analysis revealed that the EVBT combined with stent placement, TACE, and sorafenib strategy was an independent predictor of favorable OS (HR = 0.18, P < 0.001).
CONCLUSION: EVBT combined with stent placement, TACE, and sorafenib might be a safe and effective palliative treatment option for MPVTT.

PMID: 29209114 [PubMed - in process]

Epidemiology and natural history of Wilson's disease in the Chinese: A territory-based study in Hong Kong between 2000 and 2016.

Thu, 12/07/2017 - 13:45
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Epidemiology and natural history of Wilson's disease in the Chinese: A territory-based study in Hong Kong between 2000 and 2016.

World J Gastroenterol. 2017 Nov 21;23(43):7716-7726

Authors: Cheung KS, Seto WK, Fung J, Mak LY, Lai CL, Yuen MF

Abstract
AIM: To investigate the epidemiology and natural history of Wilson's disease in the Chinese.
METHODS: Data were retrieved via electronic search of hospital medical registry of the Hong Kong Hospital Authority, which covers all the public healthcare services. We identified cases of Wilson's disease between 2000 and 2016 by the International Classification of Diseases (ICD)-9 code. We analyzed the incidence rate, prevalence and adverse outcomes of Wilson's disease.
RESULTS: We identified 211 patients (male cases 104; female cases 107; median age 27.2 years, IQR: 17.1-38.6 years; duration of follow-up 8.0 years, IQR: 5.0-14.0 years). The average annual incidence rate was 1.44 per million person-years while the prevalence was 17.93 per million. Between 2000 and 2016, there was a decrease in the annual incidence rate from 1.65 to 1.23 per million person-years (P = 0.010), whereas there was an increase in the annual prevalence from 7.80 to 25.20 per million (P < 0.001). Among the 176 cases with hepatic involvement, 38 (21.6%) had cirrhosis, three (1.7%) developed hepatocellular carcinoma, 24 (13.6%) underwent liver transplantations, and 26 (14.8%) died. Seven patients had concomitant chronic viral hepatitis B or C. The 5-year and 10-years rates of overall survival were 92.6% and 89.5%, and for transplant-free survival rates 91.8% and 87.4%, respectively. Cirrhosis and possibly chronic viral hepatitis were associated with poorer overall survival.
CONCLUSION: There was a significant increase in the prevalence of Wilson's disease in Hong Kong. The prognosis was favorable except for those with cirrhosis or concomitant viral hepatitis.

PMID: 29209112 [PubMed - in process]

CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma.

Thu, 12/07/2017 - 13:45
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CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma.

Sci Rep. 2017 Dec 05;7(1):16975

Authors: Loosen SH, Roderburg C, Kauertz KL, Koch A, Vucur M, Schneider AT, Binnebösel M, Ulmer TF, Lurje G, Schoening W, Tacke F, Trautwein C, Longerich T, Dejong CH, Neumann UP, Luedde T

Abstract
Cholangiocarcinoma (CCA) represents a rare form of primary liver cancer with increasing incidence but dismal prognosis. Surgical treatment has remained the only potentially curative treatment option, but it remains unclear which patients benefit most from liver surgery, highlighting the need for new preoperative stratification strategies. In clinical routine, CA19-9 represents the most widely used tumor marker in CCA patients. However, data on the prognostic value of CA19-9 in CCA patients are limited and often inconclusive, mostly due to small cohort sizes. Here, we investigated the prognostic value of CA19-9 in comparison with other standard laboratory markers in a large cohort of CCA patients that underwent tumor resection. Of note, while CA19-9 and CEA were able to discriminate between CCA and healthy controls, CEA showed a higher accuracy for the differentiation between CCA and patients with primary sclerosing cholangitis (PSC) compared to CA19-9. Furthermore, patients with elevated levels of C-reactive protein (CRP), CA19-9 or CEA showed a significantly impaired survival in Kaplan-Meier curve analysis, but surprisingly, only CEA but not CA19-9 represented an independent predictor of survival in multivariate Cox-regression analysis. Our data suggest that CEA might help to identify CCA patients with an unfavourable prognosis after tumor resection.

PMID: 29208940 [PubMed - in process]

Alcohol Relapse After Liver Transplantation: Younger Women Are at Greatest Risk.

Thu, 12/07/2017 - 13:45
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Alcohol Relapse After Liver Transplantation: Younger Women Are at Greatest Risk.

Ann Transplant. 2017 Dec 05;22:725-729

Authors: Zeair S, Cyprys S, Wiśniewska H, Bugajska K, Parczewski M, Wawrzynowicz-Syczewska M

PMID: 29208851 [PubMed - in process]

Relaxing Access to Liver Transplantation with Living Donation: A Foolish Move or a Time to Change?

Thu, 12/07/2017 - 13:45
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Relaxing Access to Liver Transplantation with Living Donation: A Foolish Move or a Time to Change?

J Hepatol. 2017 Dec 02;:

Authors: O'Grady JG

PMID: 29208489 [PubMed - as supplied by publisher]

Response to transarterial chemoembolization may serve as selection criteria for hepatocellular carcinoma liver transplantation.

Thu, 12/07/2017 - 13:45
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Response to transarterial chemoembolization may serve as selection criteria for hepatocellular carcinoma liver transplantation.

Oncotarget. 2017 Oct 31;8(53):91328-91342

Authors: Lei J, Zhong J, Luo Y, Yan L, Zhu J, Wang W, Li B, Wen T, Yang J, Liver Surgery Group

Abstract
Aims: This study sought to extend the inclusion criteria for hepatocellular carcinoma (HCC) liver transplantation (LT), particularly addressing the safety and effectiveness of pre-LT transarterial chemoembolization (TACE).
Materials and Methods: Our study included 115 patients with HCC who underwent LT after TACE. The response measured after each TACE session was based on the mRECIST criteria: complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). We defined CR and PR patients as responders (64 cases) and SD and PD patients as non-responders (51 cases).
Results: The majority of responders could be identified after the first or second TACE sessions (57 cases, 89.1%). Overall survival rates at 1, 3 and 5 years were 95.3%, 89.1% and 75.0%, respectively, in the responder group, and these rates were much higher than those in the non-responder group (86.3%, 66.7% and 54.9%, P=0.016). In addition, the tumor-free survival rate in the responder group was also higher than in the non-responder group (P=0.009). In the responder group, a statistically improved long-term outcome was observed in patients whose HCC did not satisfy the Milan criteria (P<0.05). Univariate and multivariate Cox analyses showed that achieving CR or PR was the best predictor of survival and tumor-free survival following TACE.
Conclusion: The response to TACE, particularly following the first two sessions, primarily and robustly predicted overall and tumor-free survival in HCC patients, particularly those whose HCC did not satisfy the Milan criteria.

PMID: 29207647 [PubMed]

A palladium(II)-saccharinate complex of terpyridine exerts higher anticancer potency and less toxicity than cisplatin in a mouse allograft model.

Thu, 12/07/2017 - 13:45
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A palladium(II)-saccharinate complex of terpyridine exerts higher anticancer potency and less toxicity than cisplatin in a mouse allograft model.

Anticancer Drugs. 2017 Sep;28(8):898-910

Authors: Cetin Y, Adiguzel Z, Polat HU, Akkoc T, Tas A, Cevatemre B, Celik G, Carikci B, Yilmaz VT, Ulukaya E, Acilan C

Abstract
The main aim of this study is to assess the safety and antitumor efficacy of a palladium(II) (Pd)-saccharinate complex with terpyridine. To characterize the Pd(II) complex in vitro, its cytotoxicity was evaluated using a water-soluble tetrazolium salt cell viability assay and the mechanism of cell death was assessed by DNA fragmentation/condensation and live cell imaging analyses. The antitumor efficacy and safety of the Pd(II) complex in-vivo were examined by analyzing reduction in tumor size, changes in body and organ weight, histopathological analysis of liver, kidney, and tumor sections, and biochemical analysis of serum in C57BL/6 mice. Our results showed that the Pd(II) complex was more cytotoxic to cancer cells than noncancer cell lines and caused cell death through apoptotic pathways. The treatment of the Pd(II) complex in tumor-bearing mice effectively reduced the tumor size at half the dose used for cisplatin. The Pd(II) complex appeared to exert less liver damage than the cisplatin-based complex on changes in the hepatic enzymes levels in the serum. Hence, the complex appears to be a potential chemotherapeutic drug with high antitumor efficacy and fewer hepatotoxic complications, providing an avenue for further studies.

PMID: 28657910 [PubMed - indexed for MEDLINE]

Targeted systemic mesenchymal stem cell delivery using hyaluronate - wheat germ agglutinin conjugate.

Thu, 12/07/2017 - 13:45
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Targeted systemic mesenchymal stem cell delivery using hyaluronate - wheat germ agglutinin conjugate.

Biomaterials. 2016 Nov;106:217-27

Authors: Kim YS, Kong WH, Kim H, Hahn SK

Abstract
A variety of receptors for hyaluronate (HA), a natural linear polysaccharide, were found in the body, which have been exploited as target sites for HA-based drug delivery systems. In this work, mesenchymal stem cells (MSCs) were surface-modified with HA - wheat germ agglutinin (WGA) conjugate for targeted systemic delivery of MSCs to the liver. WGA was conjugated to HA by coupling reaction between aldehyde-modified HA and amine group of WGA. The conjugation of WGA to HA was corroborated by gel permeation chromatography (GPC) and the successful surface modification of MSCs with HA-WGA conjugate was confirmed by confocal microscopy. The synthesized HA-WGA conjugate could be incorporated onto the cellular membrane by agglutinating the cell-associated carbohydrates. Fluorescent imaging for in vivo biodistribution visualized the targeted delivery of the HA-WGA/MSC complex to the liver after intravenous injection. This new strategy for targeted delivery of MSCs using HA-WGA conjugate might be successfully exploited for various regenerative medicines including cell therapy.

PMID: 27569867 [PubMed - indexed for MEDLINE]

Liver Transplantation in Patients with Alcoholic Liver Disease: A Retrospective Study.

Wed, 12/06/2017 - 13:45
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Liver Transplantation in Patients with Alcoholic Liver Disease: A Retrospective Study.

Alcohol Alcohol. 2017 Dec 01;:1-6

Authors: Vassallo GA, Tarli C, Rando MM, Mosoni C, Mirijello A, Agyei-Nkansah A, Antonelli M, Sestito L, Perotti G, Di Giuda D, Agnes S, Grieco A, Gasbarrini A, Addolorato G, Gemelli OLT Group

Abstract
Aim: Alcoholic liver disease (ALD) is the most common liver disease in the Western World. Liver transplantation (LT) is the treatment for end-stage ALD. However, many transplant centers are still reluctant to transplant these patients because of the risk of alcohol relapse, recurrence of the primary liver disease and associated post-transplant complications. We examined survival rate, prevalence of primary liver disease recurrence, re-transplantation and post-transplant complications among transplanted patients for alcoholic cirrhosis compared with those transplanted for viral cirrhosis.
Methods: data about patients transplanted for alcoholic and viral cirrhosis at the Gemelli Hospital from January 1995 to April 2016 were retrospectively collected. Survival rate was evaluated according to the Kaplan-Meier method. Recurrence was defined as histological evidence of primary liver disease. Data on the onset of complication, causes of death and graft failure after liver transplant were analyzed.
Results: There was no statistically significant difference regarding survival rate between the two groups. Only patients transplanted for viral cirrhosis presented with primary liver disease recurrence. There was a higher rate of cancer development in patients transplanted for alcoholic cirrhosis. Cancer was the major cause of death in this population. Risk factors associated with the onset of cancer were a high MELD score at the transplant time and smoking after transplantation.
Conclusion: ALD is a good indication for LT. Patients transplanted for alcoholic cirrhosis should receive regular cancer screening and should be advised against smoking.
Short Summary: No difference was found between patients transplanted for alcoholic cirrhosis and viral cirrhosis in term of survival rate. Only patients transplanted for viral cirrhosis presented primary liver disease recurrence. A higher rate of cancer development was found in patients transplanted for alcoholic cirrohosis. This complication was associated with post-trasplant smoking.

PMID: 29206894 [PubMed - as supplied by publisher]

Development of an organ failure score in acute liver failure for transplant selection and identification of patients at high risk of futility.

Wed, 12/06/2017 - 13:45
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Development of an organ failure score in acute liver failure for transplant selection and identification of patients at high risk of futility.

PLoS One. 2017;12(12):e0188151

Authors: Figorilli F, Putignano A, Roux O, Houssel-Debry P, Francoz C, Paugam-Burtz C, Soubrane O, Agarwal B, Durand F, Jalan R

Abstract
INTRODUCTION: King's College Hospital criteria are currently used to select liver transplant candidates in acetaminophen-related acute liver failure (ALF). Although widely accepted, they show a poor sensitivity in predicting pre-transplant mortality and cannot predict the outcome after surgery. In this study we aimed to develop a new prognostic score that can allow patient selection for liver transplantation more appropriately and identify patients at high risk of futile transplantation.
METHODS: We analysed consecutive patients admitted to the Royal Free and Beaujon Hospitals between 1990 and 2015. Clinical and laboratory data at admission were collected. Predictors of 3-month mortality in the non-transplanted patients admitted to the Royal Free Hospital were used to develop the new score, which was then validated against the Beaujon cohort. The Beaujon-transplanted group was also used to assess the ability of the new score in identifying patients at high risk of transplant futility.
RESULTS: 152 patients were included of who 44 were transplanted. SOFA, CLIF-C OF and CLIF-ACLF scores were the best predictors of 3-month mortality among non-transplanted patients. CLIF-C OF score and high dosages of norepinephrine requirement were the only significant predictors of 3-month mortality in the non-transplanted patients, and therefore were included in the ALF-OFs score. In non-transplanted patients, ALF-OFs showed good performance in both exploratory (AUC = 0.89; sensitivity = 82.6%; specificity = 89.5%) and the validation cohort (AUC = 0.988; sensitivity = 100%; specificity = 92.3%). ALF-OFs score was also able to identify patients at high risk of transplant futility (AUC = 0.917; sensitivity = 100%; specificity = 79.2%).
CONCLUSION: ALF-OFs is a new prognostic score in acetaminophen-related ALF that can predict both the need for liver transplant and high risk of transplant futility, improving candidate selection for liver transplantation.

PMID: 29206839 [PubMed - in process]

HCV Therapy in Decompensated Cirrhosis before or after Liver Transplantation: A Paradoxical Quandary.

Wed, 12/06/2017 - 13:45
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HCV Therapy in Decompensated Cirrhosis before or after Liver Transplantation: A Paradoxical Quandary.

Am J Gastroenterol. 2017 Dec 05;:

Authors: Bunchorntavakul C, Reddy KR

PMID: 29206818 [PubMed - as supplied by publisher]

Hepatobiliary Hands of Hopkins.

Wed, 12/06/2017 - 13:45
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Hepatobiliary Hands of Hopkins.

Ann Surg. 2017 Dec 04;:

Authors: Pitt HA

Abstract
OBJECTIVE: This historical perspective documents the role that John L. Cameron played in advancing hepatobiliary research, education, and surgery at Johns Hopkins in the 1970s, 1980s, and 1990s.
SUMMARY OF BACKGROUND DATA: Dating back to William S. Halsted in the 19th century, leaders of the Department of Surgery at Johns Hopkins have been interested in hepatobiliary disease and surgery. John L. Cameron had broad hepato-pancreato-biliary (HPB) interests when he completed his surgical training. Over the next 3 decades, he focused on the pancreas. As a result, many faculty and trainee hepatobiliary careers were launched.
METHODS: This perspective is based on 18 years of service as a surgical resident and faculty member at Johns Hopkins. An extensive literature search on the hepatobiliary publications of Halsted, Trimble, Blalock, Longmire, Zuidema, and Cameron was undertaken for this manuscript. Numerous hepatobiliary publications from Johns Hopkins from the 1970s, 1980s, 1990s, and early 2000s were also reviewed.
RESULTS: John L. Cameron's early biliary interests included stones, infections, malignancies, and strictures. He was innovative with respect to portal hypertension and Budd-Chiari surgery and supportive when liver transplantation emerged in the 1980s. Volume-outcome studies in the 1990s included hepatic and complex biliary surgery. He supported and encouraged studies of biliary lithotripsy, laparoscopic cholecystectomy, clinical pathways, hepatobiliary cysts, and gallstone pathogenesis.
CONCLUSION: Lessons learned by many who worked with John L. Cameron included the importance of mentorship, innovation, friendship, and collaboration. He taught leadership and change management by example. He fostered a multidisciplinary approach and encouraged randomized controlled trials.

PMID: 29206676 [PubMed - as supplied by publisher]

The need and opportunity for donation after circulatory death worldwide.

Wed, 12/06/2017 - 13:45
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The need and opportunity for donation after circulatory death worldwide.

Curr Opin Organ Transplant. 2017 Dec 04;:

Authors: Manyalich M, Nelson H, Delmonico FL

Abstract
PURPOSE OF REVIEW: The global shortage of organ donors will not be resolved solely by relying on deceased donation following a brain death determination (DBD). Expansion of deceased donation after circulatory death (DCD) will be needed to address the shortfall of organs for transplantation. Approximately 120 000 organ transplants are performed each year; however, the WHO estimates that this number of transplants only resolves 10% of the annual worldwide transplant need.
RECENT FINDINGS: The report addresses the opportunity of DCD expansion by evaluating the DCD potential that is not being realized, the utility of DCD enabling DBD to emerge in some clinical situations, by the effectiveness of a donor registry in achieving DCD, and by the current clinical research of heart, lung, and liver transplantation from DCD.
SUMMARY: The future of deceased donation must include DCD and ex-vivo organ repair if the organ shortage is to be reconciled even partially to the ongoing demand. Although the religious and legal impediments have been overcome to determine brain death, the possibility of DCD has not been addressed. A program of DCD is feasible in all countries with transplantation services. The excellent results following kidney and lung transplantation suggest opportunities of heart and liver transplantation should be the focus of needed DCD accomplishment in the near future.

PMID: 29206661 [PubMed - as supplied by publisher]

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