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Invasive Fungal Disease in Pediatric Solid Organ Transplant Recipients.

Wed, 10/11/2017 - 12:45

Invasive Fungal Disease in Pediatric Solid Organ Transplant Recipients.

J Pediatric Infect Dis Soc. 2017 Jun 15;:

Authors: Saxena S, Gee J, Klieger S, Kajon A, Petersen H, Zaoutis T, Fisher B

Abstract
Background: Solid organ transplant (SOT) recipients are at risk for invasive fungal disease (IFD). Data on IFD burden in pediatric patients are limited. We aimed to determine the incidence and outcome of IFD in a large cohort of pediatric patients who underwent SOT.
Methods: A single-center cohort of pediatric patients who underwent SOT between 2000 and 2013 was assembled retrospectively. The patients were followed for 180 days after transplant or until death to determine the presence or absence of IFD. The 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group criteria were used to define IFD as proven or probable. The incidence of IFD, all-cause mortality rate, and case-fatality rate at 180 days were calculated.
Results: Among 584 pediatric patients who underwent SOT, 13 patients sustained 14 episodes of IFD (candidiasis, aspergillosis, and mucormycosis). The overall incidence was 2.2% (14.3 IFD events per 100000 patient-days). The IFD rates according to transplant type were 12.5% (1 of 8) (heart/lung), 11.4% (4 of 35) (lung), 4.7% (8 of 172) (liver), 0% (0 of 234) (kidney), and 0% (0 of 135) (heart). Three patients with IFD (2 lung and 1 heart/lung) died, and all these deaths were deemed likely attributable to the IFD; the case-fatality rate was 21.4% (3 of 14).
Conclusions: The overall incidence of IFD in these pediatric SOT recipients was low but varied across transplant type, with heart/lung and lung recipients having the highest IFD rate. Given the attributable case-fatality rate, the risk of death resulting from IFD is potentially high. More data on groups at higher risk, such as lung transplant recipients, are needed to guide targeted antifungal prophylaxis.

PMID: 28992290 [PubMed - as supplied by publisher]

Metabolic imaging of fatty kidney in diabesity: validation and dietary intervention.

Wed, 10/11/2017 - 12:45

Metabolic imaging of fatty kidney in diabesity: validation and dietary intervention.

Nephrol Dial Transplant. 2017 Sep 15;:

Authors: Jonker JT, de Heer P, Engelse MA, van Rossenberg EH, Klessens CQF, Baelde HJ, Bajema IM, Koopmans SJ, Coelho PG, Streefland TCM, Webb AG, Dekkers IA, Rabelink TJ, Rensen PCN, Lamb HJ, de Vries APJ

Abstract
Background: Obesity and type 2 diabetes have not only been linked to fatty liver, but also to fatty kidney and chronic kidney disease. Since non-invasive tools are lacking to study fatty kidney in clinical studies, we explored agreement between proton magnetic resonance spectroscopy ( 1 H-MRS) and enzymatic assessment of renal triglyceride content (without and with dietary intervention). We further studied the correlation between fatty kidney and fatty liver.
Methods: Triglyceride content in the renal cortex was measured by 1 H-MRS on a 7-Tesla scanner in 27 pigs, among which 15 minipigs had been randomized to a 7-month control diet, cafeteria diet (CAF) or CAF with low-dose streptozocin (CAF-S) to induce insulin-independent diabetes. Renal biopsies were taken from corresponding MRS-voxel locations. Additionally, liver biopsies were taken and triglyceride content in all biopsies was measured by enzymatic assay.
Results: Renal triglyceride content measured by 1 H-MRS and enzymatic assay correlated positively ( r = 0.86, P < 0.0001). Compared with control diet-fed minipigs, renal triglyceride content was higher in CAF-S-fed minipigs (137 ± 51 nmol/mg protein, mean ± standard error of the mean, P < 0.05), but not in CAF-fed minipigs (60 ± 10 nmol/mg protein) compared with controls (40 ± 6 nmol/mg protein). Triglyceride contents in liver and kidney biopsies were strongly correlated ( r = 0.97, P < 0.001).
Conclusions: Non-invasive measurement of renal triglyceride content by 1 H-MRS closely predicts triglyceride content as measured enzymatically in biopsies, and fatty kidney appears to develop parallel to fatty liver. 1 H-MRS may be a valuable tool to explore the role of fatty kidney in obesity and type 2 diabetic nephropathy in humans in vivo .

PMID: 28992141 [PubMed - as supplied by publisher]

Sensitizing Surgeons to Their Outcome Has No Measurable Short-term Benefit.

Wed, 10/11/2017 - 12:45

Sensitizing Surgeons to Their Outcome Has No Measurable Short-term Benefit.

Ann Surg. 2017 Nov;266(5):884-889

Authors: Cauchy F, Farges O, Vibert E, Boleslawski E, Pruvot FR, Regimbeau JM, Mabrut JY, Scatton O, Adham M, Laurent C, Grégoire E, Delpero JR, Bachellier P, Soubrane O

Abstract
OBJECTIVE: Investigate if involving surgeons in outcome prediction-research and having them use a dedicated Electronic-Health-Record that provides feedback, improves patients' outcome.
BACKGROUND: Improvement of clinical outcome mainly relies on the declaration of adverse events, identification of their predictors, self-assessment, and feedback.
METHODS: Thirteen French Hepato-Pancreato-Biliary-centers made commitment to include all patients undergoing elective hepatectomies in an observational study. Each center was given access to a dedicated website, where perioperative data were prospectively collected. The website provided real-time individual and comparative feedback of outcome and was also intended to perform prognostication studies. The hypothesis was that by using this strategy, the length-of-stay would be reduced by 10%. Power-calculation implied the inclusion of 1720 patients. Secondary endpoints were 90-day mortality, severe morbidity, and the comprehensive-complication index.
RESULTS: Only 5 of the 13 participating centers were fully compliant in enrolling their patients and the inclusion period was extended by 1-year (October 2012-October 2015) to meet the objective. During this period, the collaborative group published 9 studies based on the study data (median impact factor = 8.327) that identified quantitative clinical variables, qualitative clinical variables, and nonclinical variables influencing outcome. For patients enrolled by the 5 active centers (n = 1752), there was no improvement in length of stay (13.3 vs 12.4 days, P = 0.287), severe complications (23.6 vs 20.5%, P = 0.134), the complication comprehensive index (24.0 vs 24.9, P = 0.448), mortality (4.1 vs 3.9%, P = 0.903), or unplanned readmissions (7.2 vs 8.4%, P = 0.665), even after adjusting for confounders.
CONCLUSION: Simply sensitizing surgeons to their outcome has no measurable short-term clinical benefit.

PMID: 28991876 [PubMed - in process]

Centro de trasplante hepático en México con bajo volumen y excelentes resultados.

Wed, 10/11/2017 - 12:45

Centro de trasplante hepático en México con bajo volumen y excelentes resultados.

Rev Invest Clin. 2017;153(4):443-451

Authors: Vilatobá M, Mercado MÁ, Contreras-Saldivar AG, Leal-Villalpando RP, Zamudio-Bautista J, García-Juárez I, Gamboa-Domínguez A

Abstract
other: El trasplante hepático ortotópico (THO) es el tratamiento de elección para la insuficiencia hepática terminal. Numerosos estudios muestran una relación inversa entre el número de procedimientos y la mortalidad operatoria. El objetivo de este estudio es mostrar los resultados de nuestro centro y determinar si puede tener resultados equiparables a los obtenidos en centros de alto volumen. Es un estudio retrospectivo en el que se analizó la información de pacientes con THO en nuestra institución, de 1985 al 31 de diciembre de 2012. Dependiendo de la fecha del THO, el estudio se dividió en tres etapas: etapa 1, de 1985 a 1999; etapa 2, de 2000 a 2007; y etapa 3, de 2008 a 2012. En las etapas 1, 2 y 3 se realizaron 22, 37 y 56 THO, respectivamente. La mortalidad perioperatoria fue menor de manera significativa en la etapa 3 en comparación con las etapas 1 y 2 (3.5 vs. 50 y 21.7%; p = 0.001). La supervivencia de los pacientes a 1 y 5 años fue mejor en la etapa 3 (94.4 y 87.8%) que en la etapa 2 (77.6 y 66.17%) y en la etapa 1 (47 y 29%) (p = 0.001). En conclusión, los resultados actuales en THO en nuestro programa son excelentes, a pesar de ser un centro de bajo volumen.
other: Orthotopic liver transplantation (OLT) is the treatment of choice for end stage liver disease. Many studies show an inverse relationship between the number of procedures and operative mortality. The objective of the study is to show the results of our center and determine if it can have comparable results to high volumen centers. This is a retrospective study which analyzed the information of patients with OLT at our institution from 1985 to December 31, 2012. Depending on date of transplantation, the study was divided into three stages. Stage 1: from 1985 to 1999. Stage 2: from 2000 to 2007. Stage 3: from 2008 to 2012. In the 1, 2 and 3 stage 22, 37 and 56 OLT were performed respectively. Perioperative mortality was significantly lower between Stage 3 vs. Stage 1 and 2 (3.5%: vs. 50% and 21.7%, p = 0.001). Patient survival was also better at 1 and 5 years at Stage 3 (94.4%, 87.8%) vs. era 2 (77.6%, 66.17%) and Stage 1 (47% and 29%) (p = 0.001). In conclusion, the present results of OLT at our program are excellent despite being a low-volume center.

PMID: 28991277 [PubMed - in process]

Angiogenesis in the Transplanted Donor Graft after Living-Donor Liver Transplantation.

Wed, 10/11/2017 - 12:45

Angiogenesis in the Transplanted Donor Graft after Living-Donor Liver Transplantation.

Transplantation. 2017 Oct 05;:

Authors: Jung DH, Moon SH, Park SJ, Kim EJ, Jang IH, Park CS, Lee JY, Cho YP, Lee SG

Abstract
BACKGROUND: There is no direct evidence for the role of angiogenesis in liver regeneration in humans. This study aimed to determine whether angiogenesis is involved in the regeneration of transplanted donor grafts in human living-donor liver transplantation (LDLT) and to examine the impact of donor graft volume on angiogenesis.
METHODS: Clinical data and liver tissue characteristics were analyzed in 4 patients who received adult-to-adult LDLT with dual left lobe grafts from 2 living donors. Liver tissues from transplanted donor grafts were obtained and immunohistochemically examined at 3-4 weeks after transplantation using the endothelial marker Ki67+ and CD31+.
RESULTS: All recipients showed recovery of normal liver function and a significant increase in the volume of engrafted left lobes after transplantation. Immunohistochemistry showed a remarkable increase in Ki67+ single hepatocyte proliferation, implying the role of hepatocytes in liver reconstitution, and a high density of blood vessels and proliferative endothelium, suggesting in vivo angiogenesis. Furthermore, we found that Ki67+ nuclei in CD31+ sinusoidal endothelial cells were higher in recipients with smaller donor grafts than in those with larger donor grafts.
CONCLUSIONS: Our results suggested that angiogenesis is involved in the regeneration of transplanted liver in humans in inverse proportion to the donor graft volume.

PMID: 28991124 [PubMed - as supplied by publisher]

Optimizing the detection of biliary dysplasia in primary sclerosing cholangitis before liver transplantation.

Wed, 10/11/2017 - 12:45

Optimizing the detection of biliary dysplasia in primary sclerosing cholangitis before liver transplantation.

Scand J Gastroenterol. 2017 Oct 09;:1-8

Authors: Majeed A, Castedal M, Arnelo U, Söderdahl G, Bergquist A, Said K

Abstract
BACKGROUND: Patients with primary sclerosing cholangitis (PSC) have increased risk of cholangiocarcinoma (CCA). We evaluated pre-transplant work-up in PSC patients, to search for the most effective strategy for the detection of biliary dysplasia or early CCA.
METHODS: Two hundred and twenty five consecutive PSC patients undergoing liver transplantation (LTx) in Sweden between 1999 and 2013 were studied. Patients with CCA or dysplasia in the explanted liver were compared with those with benign histopathology. Measures of test performance were calculated for patients having brush cytology on one endoscopic retrograde cholangiopancreaticography (ERCP) occasion, for those having repeated examinations with or without cholangioscopy, and for fluorescence in situ hybridization (FISH). Survival after LTx was analyzed.
RESULTS: Brush cytology on a single ERCP occasion had moderate sensitivity (57%) and high specificity (94%) for the detection of CCA/high grade dysplasia (HGD) in the explanted liver. The corresponding sensitivity and specificity for FISH were 84% and 90%, respectively. Utilizing repeated ERCP and brush cytology to confirm the initial finding improved sensitivity to 82%. Using single operator cholangioscopy (SOC) for targeted examination at the second ERCP improved sensitivity (100%) and specificity (97%) significantly. Mortality rate in patients with incidentally discovered CCA (n = 16) in the explanted liver was significantly higher than in patients with HGD or benign histopathology (HR 16.0; 95% CI, 5.6-45.4; p < .001).
CONCLUSIONS: Repeated brush cytology especially when combined with targeted examination under SOC guidance is superior to single brush examinations. This strategy improves the detection of malignancy in PSC and is of importance for selection of patients for LTx.

PMID: 28990806 [PubMed - as supplied by publisher]

Gut microbiota as a therapeutic target for metabolic disorders.

Wed, 10/11/2017 - 12:45

Gut microbiota as a therapeutic target for metabolic disorders.

Curr Med Chem. 2017 Oct 09;:

Authors: Okubo H, Nakatsu Y, Kushiyama A, Yamamotoya T, Matsunaga Y, Inoue MK, Fujishiro M, Sakoda H, Ohno H, Yoneda M, Ono H, Asano T

Abstract
The prevalence of metabolic disorders has been rising worldwide, making the identification of factors affecting metabolic control more important than ever. Gut microbiota play a vital role not only in the digestion and absorption of nutrients, but also in homeostatic maintenance of host immunity, metabolism and the gut barrier. It was recently suggested that gut microbiota alterations contribute to the pathogenesis of metabolic disorders such as obesity, diabetes mellitus and non-alcoholic fatty liver disease. Possible causal links between gut microbiota and these metabolic disorders, as well as the underlying mechanisms, have been the focus of both clinical and basic research. Although further studies are needed, the gut microbiota represents a novel potential therapeutic target for a range of metabolic disorders. In this review, we discuss relationships between the gut microbiota and metabolic disorders, and also promising interventions such as prebiotics, probiotics, fecal microbiota transplantation, and other new treatment possibilities, focusing especially on recent human studies.

PMID: 28990516 [PubMed - as supplied by publisher]

Correlation between plasma fibrinogen and FIBTEM thromboelastometry during liver transplantation: a comprehensive assessment.

Wed, 10/11/2017 - 12:45

Correlation between plasma fibrinogen and FIBTEM thromboelastometry during liver transplantation: a comprehensive assessment.

Vox Sang. 2017 Oct 08;:

Authors: Blasi A, Sabate A, Beltran J, Costa M, Reyes R, Torres F

Abstract
BACKGROUND: Thromboelastometry may reduce red blood cell (RBC) transfusion in liver transplantation (LT). Fibrinogen concentration is a primary determinant of FIBTEM maximum clot firmness (MCF), but several factors could affect the correlation between FIBTEM MCF and fibrinogen values. We aimed to investigate (1) the concordance between fibrinogen level and FIBTEM MCF and (2) the association of fibrinogen level and FIBTEM MCF with RBC transfusion during LT.
METHODS: A post hoc analysis of data from a randomized, multicentre, double-blind, saline/fibrinogen trial was used (NCT01539057). A total of 86 adult patients were included.
RESULTS: The Lin concordance coefficient (LCC) between FIBTEM MCF and fibrinogen levels with the model formula 1·3679 + 0·05414* FIBTEM MCF was poor overall (LLC [95% CI]: 0·387 [0·340 to 0·432]) and moderate for the preperfusion period (LLC [95% CI]: 0·789 [0·747 to 0·824]), but very poor for the postreperfusion period (LLC [95% CI] 0·170 [0·105 to 0·233]). The model assessed for RBC transfusion for FIBTEM MCF showed an area under the curve of 0·788 [0·745-0·832]. Patients with FIBTEM MCF values <8 mm had a significantly higher likelihood of receiving RBC than patients with higher values. (OR [95% CI]: 2·08 [1·30-3·33], P = 0·002). FIBTEM MCF values over 10 mm do not appear to reduce the likelihood of RBC transfusion.
CONCLUSION: FIBTEM MCF is not a good indicator of plasma fibrinogen values after graft reperfusion. FIBTEM MCF >8 mm during the LT procedure is associated with less RBC transfusion. FIBTEM MCF values over 10 mm could lead to unnecessary fibrinogen administration.

PMID: 28990201 [PubMed - as supplied by publisher]

Diaphragmatic hernia following liver resection: case series and review of the literature.

Wed, 10/11/2017 - 12:45

Diaphragmatic hernia following liver resection: case series and review of the literature.

Ann Hepatobiliary Pancreat Surg. 2017 Aug;21(3):114-121

Authors: Esposito F, Lim C, Salloum C, Osseis M, Lahat E, Compagnon P, Azoulay D

Abstract
BACKGROUNDS/AIMS: Postoperative diaphragmatic hernia, following liver resection, is a rare complication.
METHODS: Data of patients who underwent major hepatectomy for liver tumors, between 2011 and 2015 were retrospectively reviewed. The literature was searched for studies reporting the occurrence of diaphragmatic hernia following liver resection.
RESULTS: Diaphragmatic hernia developed in 2.3% of patients (3/131) with a median delay of 14 months (4-31 months). One patient underwent emergency laparotomy for bowel obstruction and two patients underwent elective diaphragmatic hernia repair. At last follow-up, no recurrences were observed. Fourteen studies including 28 patients were identified in the literature search (donor hepatectomy, n=11: hepatectomy for liver tumors, n=17). Diaphragmatic hernia was repaired emergently in 42.9% of cases and digestive resection was necessary in 28.5% of the cases. One patient died 3 months after hepatectomy, secondary to sepsis, from a segment of small bowel that perforated into the diaphragmatic hernia.
CONCLUSIONS: Although rare, diaphragmatic hernia should be considered as an important complication, especially in living donor liver transplant patients. Diaphragmatic hernia should be repaired surgically, even for asymptomatic patients.

PMID: 28989997 [PubMed]

Impact of time to surgery in the outcome of patients with liver resection for BCLC 0-A stage hepatocellular carcinoma.

Wed, 10/11/2017 - 12:45

Impact of time to surgery in the outcome of patients with liver resection for BCLC 0-A stage hepatocellular carcinoma.

J Hepatol. 2017 Oct 05;:

Authors: Lim C, Bhangui P, Salloum C, Gavara CG, Lahat E, Luciani A, Compagnon P, Calderaro J, Feray C, Azoulay D

Abstract
BACKGROUND & AIMS: The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend resection for very early and early single hepatocellular carcinoma (HCC) patients. It is not known whether a delay in resection from the time of diagnosis (the time-to-surgery (TTS), i.e., the elapsed time from diagnosis to surgery) affects outcomes. We aim to evaluate the impact of TTS on the recurrence and survival outcomes.
METHODS: All patients resected for BCLC stage 0-A single HCC from 2006 to 2016 were studied to evaluate the impact of TTS on recurrence rate, recurrence-free survival (RFS), transplantability following recurrence, and intention-to-treat overall survival (ITT-OS). Propensity score matching (PSM) was further performed to ensure comparability.
RESULTS: The study population included 100 patients. Surgery was performed between 0.6 and 77 months after diagnosis (median TTS: 3 months; interquartile range: 1.8 - 4.6 months). There was no post-operative mortality. Patients with TTS ≥ 3 months (70% of these patients had TTS 3-6 months) compared to those with TTS < 3 months had a higher post-operative morbidity (36% vs. 16%, p = 0.02), a similar tumor recurrence rate (32% vs. 32%, p = 1.00), RFS (37% vs. 48%, p = 0.42), transplantability following tumor recurrence (63% vs. 50% p = 0.48), and 5-year ITT-OS (82% vs. 80%, p = 0.20). Similar results were observed after PSM.
CONCLUSION: Patients with BCLC stage 0-A single HCC can undergo surgery with TTS ≥ 3 months without impaired oncologic outcomes. An increase in the TTS within a safe range could allow time for proper evaluation before surgery, and ethical testing of new neoadjuvant treatments aiming to reduce the high rate of tumor recurrence despite curative resection.
LAY SUMMARY: A delay of ≥ 3 months in time to resection after diagnosis in HCC patients meeting the European Association for the Study of Liver Disease/American Association for the Study of Liver Disease criteria for resection does not affect oncological and long-term outcomes compared to those with a delay to surgery of < 3 months.

PMID: 28989094 [PubMed - as supplied by publisher]

Metroticket 2.0 Model for Analysis of Competing Risks of Death Following Liver Transplantation for Hepatocellular Carcinoma.

Wed, 10/11/2017 - 12:45

Metroticket 2.0 Model for Analysis of Competing Risks of Death Following Liver Transplantation for Hepatocellular Carcinoma.

Gastroenterology. 2017 Oct 05;:

Authors: Mazzaferro V, Sposito C, Zhou J, Pinna AD, De Carlis L, Fan J, Cescon M, Di Sandro S, Yi-Feng H, Lauterio A, Bongini M, Cucchetti A

Abstract
BACKGROUND & AIMS: Outcomes of liver transplantation for hepatocellular carcinoma (HCC) are determined by cancer-related and non-related events. Treatments for hepatitis C virus (HCV) infection have reduced non-cancer events among patients receiving liver transplants, so reducing HCC-related death might be an actionable endpoint. We performed a competing risk analysis to evaluate factors associated with survival of patients with HCC, and developed a prognostic model based on features of HCC patients before liver transplantation.
METHODS: We performed multivariable competing risk regression analysis to identify factors associated with HCC-specific death of patients who underwent liver transplantation. The training set comprised 1018 patients who underwent liver transplantation for HCC from January 2000 through December 2013 at 3 tertiary centers in Italy. The validation set comprised 341 consecutive patients who underwent liver transplantation for HCC during the same period at the Liver Cancer Institute in Shanghai, China. We collected pre-transplant data on etiology of liver disease, number and size of tumors, patient level of alpha-fetoprotein (AFP), model for end-stage liver disease score, tumor stage, numbers and types of treatment, response to treatments, tumor grade, micro-vascular invasion, dates and causes of death. Death was defined as HCC-specific when related to HCC recurrence after transplant, disseminated extra- and/or intra-hepatic tumor relapse and worsened liver function in presence of tumor spread. The cumulative incidence of death was segregated for HCV status.
RESULTS: In the competing-risk regression, the sum of tumor number and size and of Log10 level of AFP were significantly associated with HCC-specific death (P<.001), returning an average c-statistic of 0.780 (95% CI, 0.763-0.798). Five-year cumulative incidence of non-HCC-related death were 8.6% in HCV-negative patients and 18.1% in HCV-positive patients. For patients with HCC to have a 70% chance of HCC-specific survival 5 years after transplantation, their level of AFP should be below 200 ng/mL and the sum of number and size of tumors (in cm) should not exceed 7; if the level of AFP was 200-400 ng/mL, the sum of the number and size of tumors should be 5 or less; if their level of AFP was 400-1000 ng/mL, the sum of the number and size of tumors should be 4 or less. In the validation set, the model identified patients who survived 5 years after liver transplantation with 0.721 accuracy (95% CI, 0.648%-0.793%). Our model, based on patients' level of AFP and HCC number and size, outperformed the Milan, UCSF, Shanghai-Fudan, Up-to-7 criteria (P<.001), and AFP French model (P=.044) to predict which patients will survive for 5 years after liver transplantation.
CONCLUSIONS: We developed a model, based on level of AFP, tumor size and tumor number, to determine risk of death from HCC-related factors after liver transplantation. This model might be used to select endpoints and refine selection criteria for liver transplantation for patients with HCC. To predict 5-years survival and risk of HCC-related death using an online calculator, please see: www.hcc-olt-metroticket.org/.

PMID: 28989060 [PubMed - as supplied by publisher]

Estimation of the future remnant liver function is a better tool to predict post-hepatectomy liver failure than platelet-based liver scores.

Wed, 10/11/2017 - 12:45

Estimation of the future remnant liver function is a better tool to predict post-hepatectomy liver failure than platelet-based liver scores.

Eur J Surg Oncol. 2017 Sep 04;:

Authors: Chapelle T, Op de Beeck B, Driessen A, Roeyen G, Bracke B, Hartman V, Huyghe I, Morrison S, Ysebaert D, Francque S

Abstract
INTRODUCTION: Recently, there has been increasing interest in the preoperative prediction and prevention of post-hepatectomy liver failure (PHLF). This is a particular concern in colorectal liver metastases (CRLM), when surgery follows potentially hepatotoxic chemotherapy. Platelet-based liver scores (PBLS) such as APRI and FIB-4 are predictive of chemotherapy-associated liver injury (CALI) and PHLF. Estimation of the future liver remnant function (eFLRF) by combining (99m)Tc-Mebrofenin Hepatobiliary Scintigraphy (HBS(BSA)) with future liver remnant volume ratio (FLRV%), is predictive of PHLF and related mortality. We hypothesized that a HBS(BSA) based formula was a better predictor for PHLF than PBLS in chemotherapy-pretreated CRLM.
METHODS: Between 2012 and 2016, 140 patients underwent liver resection for CRLM following systemic therapy. HBS(BSA), FLRV%, eFLRF and PBLS were calculated and compared for their value in predicting PHLF.
RESULTS: eFLRF and FLRV% had a better predictive value for PHLF than HBS(BSA) alone and APRI and FIB-4 (AUC = 0.800, 0.843 versus 0.652, 0.635 and 0.658 respectively). In a subgroup analysis (Oxaliplatin all, Oxaliplatin ≥ 6 cycles, Irinotecan all and Irinotecan ≥ 6 cycles), eFLRF was the only factor predictive for PHLF in all subgroups (all: p ≤ 0.05). Prediction of HBS(BSA) for chemotherapy associated steato-hepatitis (CASH) reached almost significance (p = 0.06). FIB-4 was predictive for sinusoidal obstruction syndrome (SOS) (p = 0.011). Only weak correlation was found between HBS(BSA) and PBLS.
CONCLUSION: eFLRF is a better predictor of PHLF than PBLS or HBS(BSA) alone. PBLS seem to measure other aspects of liver function or damage than HBS(BSA).

PMID: 28988766 [PubMed - as supplied by publisher]

Cost of achieving equivalent outcomes in sicker patients after liver transplant.

Wed, 10/11/2017 - 12:45

Cost of achieving equivalent outcomes in sicker patients after liver transplant.

HPB (Oxford). 2017 Oct 04;:

Authors: Dhar VK, Wima K, Kim Y, Hoehn RS, Jung AD, Ertel AE, Diwan TS, Paterno F, Shah SA

Abstract
BACKGROUND: We aimed to characterize variability in cost after straightforward orthotopic liver transplant (OLT).
METHODS: Using the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified patients who underwent OLT between 2011 and 2014. Patients meeting criteria for straightforward OLT, defined as length of stay < 14 days with discharge to home, were selected (n = 5763) and grouped into tertiles (low, medium, high) according to cost of perioperative stay.
RESULTS: Patients undergoing straightforward OLT were of similar demographics regardless of cost. High cost patients were more likely to require preoperative hemodialysis, had higher severity of illness, and higher model for end-stage liver disease (MELD) (p < 0.01). High cost patients required greater utilization of resources including lab tests, blood transfusions, and opioids (p < 0.01). Despite having higher burden of disease and requiring increased resource utilization, high cost OLT patients with a straightforward perioperative course were shown to have identical 2-year graft and overall survival compared to lower cost patients (p = 0.82 and p = 0.63), respectively.
CONCLUSION: Providing adequate perioperative care for OLT patients with higher severity of illness and disease burden requires increased cost and resource utilization; however, doing so provides these patients with long term survival equivalent to more routine patients.

PMID: 28988703 [PubMed - as supplied by publisher]

Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors - a multi-institutional study.

Wed, 10/11/2017 - 12:45

Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors - a multi-institutional study.

HPB (Oxford). 2017 Oct 05;:

Authors: Sallinen VJ, Le Large TTY, Tieftrunk E, Galeev S, Kovalenko Z, Haugvik SP, Antila A, Franklin O, Martinez-Moneo E, Robinson SM, Panzuto F, Regenet N, Muffatti F, Partelli S, Wiese D, Ruszniewski P, Dousset B, Edwin B, Bartsch DK, Sauvanet A, Massimo F, Ceyhan GO, Gaujoux S, Pancreas 2000 research group

Abstract
BACKGROUND: Malignant potential of small (≤20 mm) nonfunctional pancreatic neuroendocrine tumors (sNF-PNET) is difficult to predict and management remain controversial. The aim of this study was to assess the prognosis of sporadic nonmetastatic sNF-PNETs.
METHODS: Patients were identified from databases of 16 centers. Outcomes and risk factors for recurrence were identified by uni- and multivariate analyses.
RESULTS: sNF-PNET was resected in 210 patients, and 66% (n = 138) were asymptomatic. Median age was 60 years, median tumor size was 15 mm, parenchyma-sparing surgery was performed in 42%. Postoperative mortality was 0.5% (n = 1), severe morbidity rate was 14.3% (n = 30), and 14 of 132 patients (10.6%) with harvested lymph nodes had metastatic lymph nodes. Tumor size, presence of biliary or pancreatic duct dilatation, and WHO grade 2-3 were independently associated with recurrence. Patients with tumors sized ≤10 mm were disease free at last follow-up. The 1-, 3- and 5-year disease-free survival rates for patients with tumors sized 11-20 mm on preoperative imaging were 95.1%, 91.0%, and 87.3%, respectively.
CONCLUSIONS: In sNF-PNETs, the presence of biliary or pancreatic duct dilatation or WHO grade 2-3 advocate for surgical treatment. In the remaining patients, a wait-and-see policy might be considered.

PMID: 28988702 [PubMed - as supplied by publisher]

Alcoholic Liver Disease: Pathogenesis and Current Management.

Wed, 10/11/2017 - 12:45

Alcoholic Liver Disease: Pathogenesis and Current Management.

Alcohol Res. 2017;38(2):147-161

Authors: Osna NA, Donohue TM, Kharbanda KK

Abstract
Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease.

PMID: 28988570 [PubMed - in process]

Glucocorticoid treatment facilitates development of a metabolic syndrome in ovariectomized Macaca Mulatta fed a high fat diet.

Wed, 10/11/2017 - 12:45

Glucocorticoid treatment facilitates development of a metabolic syndrome in ovariectomized Macaca Mulatta fed a high fat diet.

Steroids. 2017 Oct 04;:

Authors: Li L, Yang G, Liao G, Mei J, Li L, Wang C, Yuan Y, Shi Y, Liu J, Zhong Z, Cheng J, Lu Y, Clarke IJ, Chen Y

Abstract
Metabolic syndrome (MetS) is characterized by a cluster of key features, which include abdominal obesity, insulin resistance, hypertension, and dyslipidemia. The aim of this study was to assess the impact of elevated glucocorticoid levels on the development of MetS in middle-aged female rhesus monkeys (Macaca Mulatta) after ovariectomy. Six female ovariectomized rhesus monkeys (9-13 years) were randomly assigned to either a control group (normal diet, n=3) or a group in which MetS was facilitated (n=3). The MetS group fed with HFD (15% fat) and received oral prednisone acetate treatment (50 mg/day). After 24 months, the GCs treatment was withdrawn with continuation of high-fat feeding for a further 12 months. After 24 months, the MetS group displayed a significant increase in body weight and abdominal circumference. Additionally, the MetS animals displayed abnormal serum lipids, insulin resistance and impaired glucose tolerance. Histology of liver biopsies indicated marked accumulation of lipid droplets in hepatocytes of MetS animals. Withdrawal of GCs treatment led to recovery from above-mentioned metabolic disorders. Whereas GCs treatment increased leptin expression, it lowered expression of adiponectin and other factors in adipose tissue. Expression of Hydroxy-steroid dehydrogenase-1 and glucose transporter type-4 in the livers of MetS animals were reduced. We conclude that in the context of high fat diet, high levels of exogenous GCs contribute to the development of MetS in non-human primates.

PMID: 28988119 [PubMed - as supplied by publisher]

Clinical impact of intrapulmonary vascular dilatation in liver transplant candidates.

Wed, 10/11/2017 - 12:45

Clinical impact of intrapulmonary vascular dilatation in liver transplant candidates.

Chest. 2017 Oct 05;:

Authors: DuBrock HM, Krowka MJ, Forde KA, Krok K, Patel M, Sharkoski T, Sprys M, Lin G, Oh JK, Mottram CD, Scanlon PD, Fallon MB, Kawut SM

Abstract
BACKGROUND: Intrapulmonary vascular dilatations (IPVD) are frequently detected in patients with liver disease by the delayed appearance of microbubbles on contrast-enhanced echocardiography. IPVD with an elevated alveolar-arterial (A-a) gradient define hepatopulmonary syndrome, however the importance of IPVD in the absence of abnormal gas exchange is unknown. We aimed to determine the clinical impact of IPVD in patients with liver disease.
METHODS: We performed a cross-sectional study within the Pulmonary Vascular Complications of Liver Disease (PVCLD2) Study, a multicenter prospective cohort study of patients being evaluated for liver transplantation. We excluded patients with obstructive or restrictive lung disease, hepatopulmonary syndrome (HPS), or intracardiac shunting. Patients with and without IPVD were compared.
RESULTS: Forty-six patients with IPVD and 81 patients without IPVD were included. Patients with IPVD were more likely to have autoimmune hepatitis and less likely to have cryptogenic cirrhosis and hepatocellular carcinoma. Patients with IPVD had higher Child-Pugh scores (6 [IQR 5-7] vs 5 [IQR 4-7], P=0.04), possibly higher MELD scores (14.5 [IQR 11.6-15.8] vs 12.1 [IQR 9.4-15.0], P=0.06), a higher partial pressure of oxygen in arterial blood (PaO2) (97.9 [IQR 92.0-103.0] mmHg vs 89.0 [IQR 82.0-96.9] mmHg, P<0.001) and lower A-a gradient (9.9 [IQR 6.2-13.5] mmHg vs 14.9 [IQR 9.0-21.8] mmHg, P<0.001). Symptoms and quality of life were similar between the groups.
CONCLUSIONS: Autoimmune hepatitis and increased liver disease severity are associated with the presence of IPVD, which is characterized by higher PaO2. Future studies to better characterize IPVD pathogenesis and the relationship of IPVD to HPS are warranted.

PMID: 28987478 [PubMed - as supplied by publisher]

Follow-up of the Post-Liver Transplantation Patient: A Primer for the Practicing Gastroenterologist.

Wed, 10/11/2017 - 12:45

Follow-up of the Post-Liver Transplantation Patient: A Primer for the Practicing Gastroenterologist.

Clin Liver Dis. 2017 Nov;21(4):793-813

Authors: Cheung A, Levitsky J

Abstract
The focus in liver transplantation in the next 10 years will likely change from preventing viral disease recurrence to minimizing the toll of rejection and fatty liver disease, minimizing the complications from immunosuppression with withdrawal strategies, and more optimal management of long-term risks, such as malignancy, cardiovascular disease, and renal failure. In addition, now that short-term results (<1 year) have improved significantly, there will be a shift toward improving long-term patient and graft survival, as well as a focus on primary care preventive strategies.

PMID: 28987263 [PubMed - in process]

Acute Liver Failure.

Wed, 10/11/2017 - 12:45

Acute Liver Failure.

Clin Liver Dis. 2017 Nov;21(4):769-792

Authors: Bunchorntavakul C, Reddy KR

Abstract
Acute liver failure (ALF) is a life-threatening condition of heterogeneous etiology. Outcomes are better with early recognition and prompt initiation of etiology-specific therapy, intensive care protocols, and liver transplantation (LT). Prognostic scoring systems include the King's College Criteria and Model for End-stage Liver Disease score. Cerebral edema and intracranial hypertension are reasons for high morbidity and mortality; hypertonic saline is suggested for patients with a high risk for developing intracranial hypertension, and when it does, mannitol is recommended as first-line therapy. Extracorporeal liver support system may serve as a bridge to LT and may increase LT-free survival in select cases.

PMID: 28987262 [PubMed - in process]

Wilson Disease: Diagnosis, Treatment, and Follow-up.

Wed, 10/11/2017 - 12:45

Wilson Disease: Diagnosis, Treatment, and Follow-up.

Clin Liver Dis. 2017 Nov;21(4):755-767

Authors: Schilsky ML

Abstract
Consideration of a diagnosis of Wilson disease is still the critical factor in testing for and establishing disease diagnosis. In association with other clinical and biochemical tests, liver biopsy results and molecular genetic testing can also be used to generate a score for diagnosing Wilson disease. Medical therapy is effective for most patients; liver transplant can rescue those with acute liver failure or those with advanced liver disease who fail to respond to or discontinue medical therapy. Treatment monitoring must be done at regular intervals and includes clinical evaluation, liver tests and blood counts, and copper metabolic parameters.

PMID: 28987261 [PubMed - in process]

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