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Association of Lymph Node Status With Survival in Patients After Liver Resection for Hilar Cholangiocarcinoma in an Italian Multicenter Analysis.

Thu, 06/22/2017 - 12:45
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Association of Lymph Node Status With Survival in Patients After Liver Resection for Hilar Cholangiocarcinoma in an Italian Multicenter Analysis.

JAMA Surg. 2016 Oct 01;151(10):916-922

Authors: Giuliante F, Ardito F, Guglielmi A, Aldrighetti L, Ferrero A, Calise F, Giulini SM, Jovine E, Breccia C, De Rose AM, Pinna AD, Nuzzo G

Abstract
Importance: The prognostic value of lymph node (LN) assessment after liver resection for hilar cholangiocarcinoma (HC) is still controversial, and the number of LNs required to be removed to obtain adequate staging is not well defined.
Objectives: To evaluate the LN status in patients after liver resection for HC and to clarify which prognostic factor (the number of positive LNs or the LN ratio [LNR]) was most accurate for staging and what minimum number of retrieved LNs was required for adequate staging.
Design, Setting, and Participants: Retrospective multicenter study of patients who underwent resection for HC between January 1, 1992, and December 31, 2007, at 8 hepatobiliary Italian centers. The last follow-up was assessed in July 2014.
Main Outcome and Measures: Differences in overall survival (OS) according to the LN status were analyzed. The OS results were defined as actual because all included patients completed a 5-year follow-up.
Results: One-hundred seventy-five patients with 1133 retrieved LNs were analyzed. The mean (SD) age of the cohort was 63 (10) years, and 42.9% (75 of 175) were female. The median number of LNs examined per patient was 6.5. Forty percent (70 of 175) had LN metastasis. An LNR exceeding 0.20 was associated with significantly lower 5-year OS than an LNR of 0.20 or less (10.6% vs 24.4%; odds ratio, 2.434; 95% CI, 1.020-5.810; P = .04). On multivariable analysis, the LNR was the only independent prognostic factor for OS but was influenced by the total number of retrieved LNs. The LNR was greater than 0.20 in all patients (30 of 30) with 1 to 4 retrieved LNs and in 52.5% (21 of 40) of patients with at least 5 retrieved LNs. Five-year OS in patients with 1 to 5 retrieved LNs was significantly lower than that in those with 6 to 7 retrieved LNs and those with at least 8 retrieved LNs (34.2%, 64.5%, and 62.7%, respectively; P = .047). Five-year OS did not significantly improve when the number of retrieved LNs was greater than 6. These results were confirmed in a receiver operating characteristic curve analysis performed among N0R0 patients, in whom 5 retrieved LNs was the most accurate cutoff to predict 5-year actual OS (area under the curve, 0.624; P = .004).
Conclusions and Relevance: An LNR exceeding 0.20 was the only independent prognostic factor for OS in N1 patients after liver resection for HC. However, the LNR was influenced by the total number of retrieved LNs, and removal of more than 5 LNs was the minimum number of LNs required for adequate staging.

PMID: 27556741 [PubMed - indexed for MEDLINE]

HCV-positive Donor Organs in Solid Organ Transplantation: "Mind the Gap!"

Wed, 06/21/2017 - 21:45

HCV-positive Donor Organs in Solid Organ Transplantation: "Mind the Gap!"

Am J Transplant. 2017 Jun 20;:

Authors: Fishman JA, Forns X

Abstract
The shortage of organs for transplantation is a major impediment to access to life-saving therapy. The availability of antiviral therapies that control hepatitis B (HBV) and HIV, or cure hepatitis C (HCV), have changed traditional equations in transplantation, allowing infected individuals access to transplantation without unimpeded viral replication during immunosuppression. The availability of these therapies also permits use of organs from donors actively or potentially infected with these viruses. This article is protected by copyright. All rights reserved.

PMID: 28632974 [PubMed - as supplied by publisher]

P4 Stump Approach for Intraoperative Portal Vein Stenting in Pediatric Living Donor Liver Transplantation: An Innovative Technique for a Challenging Problem.

Wed, 06/21/2017 - 21:45

P4 Stump Approach for Intraoperative Portal Vein Stenting in Pediatric Living Donor Liver Transplantation: An Innovative Technique for a Challenging Problem.

Ann Surg. 2017 Jun 19;:

Authors: Chen CL, Cheng YF, Huang V, Lin TL, Chan YC, Ou HY, Yong CC, Wang SH, Lin CC

Abstract
OBJECTIVE: The aim of this study was to evaluate the utility of the P4 stump stenting approach for treating portal vein (PV) complications in pediatric living donor liver transplantation (LDLT).
BACKGROUND: PV complications cause significant morbidity and mortality in pediatric LDLT. Biliary atresia in the backdrop of pathological PV hypoplasia and sclerosis heightens the complexity of PV reconstruction. The authors developed a novel approach for intraoperative PV stenting via the graft segment 4 PV stump (P4 stump) to address this challenge.
METHODS: From April 2009 to December 2016, 15 pediatric LDLT recipients (mean age 10.3 ± 5.0 months, mean graft-recipient weight ratio 3.70%) underwent intraoperative stenting for suboptimal PV flow (<10 cm/s) or PV occlusion after collateral ligation and graft repositioning. Under portography, metallic stents were deployed via the reopened P4 stump of the left lateral segment grafts.
RESULTS: PV diameter and peak flow increased significantly after stent placement (2.93 ± 1.74 to 7.01 ± 0.91 mm and 2.0 ± 9.2 to 17.3 ± 3.5 cm/s, respectively, P = 0.001 for both), and there were no technical failures. Stents in all surviving patients remained patent up to 8 years (mean 27.7 months), with no vascular or biliary complications. After implementation of the P4 approach, the incidence of variceal bleeding as a late complication decreased from 7% to zero.
CONCLUSION: The P4 stump stenting approach affords procedural convenience, ease of manipulation, and consistent results with the potential for excellent long-term patency in children despite continued growth. This technique obviates the need for more demanding post-transplant stenting, and may become a substitute for complicated revision surgery, portosystemic shunting, or retransplantation.

PMID: 28632515 [PubMed - as supplied by publisher]

Reply to: External Validation of the Donor Risk Index and the Eurotransplant Donor Risk Index on the French Liver Transplantation registry.

Wed, 06/21/2017 - 21:45

Reply to: External Validation of the Donor Risk Index and the Eurotransplant Donor Risk Index on the French Liver Transplantation registry.

Liver Int. 2017 Jun 20;:

Authors: Blok JJ, Putter H, de Boer JD, Braat AE

Abstract
With interest we read the recent publication by Winter et al. [1] In their publication the authors describe the inability to validate the donor risk index (DRI) [2] and Eurotransplant donor risk index (ET-DRI) [3] with data from the French liver transplant (LT) registry. The intention of the authors to validate the DRI/ET-DRI for use as an indicator of donor risk and subsequently to improve matching between liver donors and LT recipients is relevant and important. This article is protected by copyright. All rights reserved.

PMID: 28632324 [PubMed - as supplied by publisher]

Ball-in-ball ZrO2 nanostructure for simultaneous CT imaging and highly efficient synergic microwave ablation and tri-stimuli-responsive chemotherapy of tumors.

Wed, 06/21/2017 - 21:45

Ball-in-ball ZrO2 nanostructure for simultaneous CT imaging and highly efficient synergic microwave ablation and tri-stimuli-responsive chemotherapy of tumors.

Nanoscale. 2017 Jun 20;:

Authors: Long D, Niu M, Tan L, Fu C, Ren X, Xu K, Zhong H, Wang J, Li L, Meng X

Abstract
Combined thermo-chemotherapy displays outstanding synergically therapeutic efficiency when compared with standalone thermotherapy and chemotherapy. Herein, we developed a smart tri-stimuli-responsive drug delivery system involving X@BB-ZrO2 NPs (X represents loaded IL, DOX, keratin and tetradecanol) based on novel ball-in-ball-structured ZrO2 nanoparticles (BB-ZrO2 NPs). The microwave energy conversion efficiency of BB-ZrO2 NPs was 41.2% higher than that of traditional single-layer NPs due to the cooperative action of self-reflection and spatial confinement effect of the special two-layer hollow nanostructure. The tri-stimuli-responsive controlled release strategy indicate that integrated pH, redox and microwaves in single NPs based on keratin and tetradecanol could effectively enhance the specific controlled release of DOX. The release of DOX was only 8.1% in PBS with pH = 7.2 and GSH = 20 μM. However, the release could reach about 50% at the tumor site (pH = 5.5, GSH = 13 mM) under microwave ablation. The as-made X@BB-ZrO2 NPs exhibited perfect synergic therapy effect of chemotherapy and microwave ablation both in subcutaneous tumors (H22 tumor-bearing mice) and deep tumors (liver transplantation VX2 tumor-bearing rabbit model). There was no recurrence and death in the X@BB-ZrO2 + MW group during the therapy of subcutaneous tumors even on the 42(nd) day. The growth rates in the deep tumor of the control, MW and X@BB-ZrO2 + MW groups were 290.1%, 14.1% and -42% 6 days after ablation, respectively. Dual-source CT was used to monitor the metabolism behavior of the as-made BB-ZrO2 NPs and traditional CT was utilized to monitor the tumor growth in rabbits. Frozen section examination and ICP results indicated the precise control of drug delivery and enhanced cytotoxicity by the tri-stimuli-responsive controlled release strategy. The ball-in-ball ZrO2 NPs with high microwave energy conversion efficiency were first developed for synergic microwave ablation and tri-stimuli-responsive chemotherapy, which may have potential applications in clinic.

PMID: 28632268 [PubMed - as supplied by publisher]

Management of pediatric hepatocellular carcinoma: A multimodal approach.

Wed, 06/21/2017 - 21:45
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Management of pediatric hepatocellular carcinoma: A multimodal approach.

Pediatr Transplant. 2017 Jun 20;:

Authors: Kohorst MA, Warad DM, Matsumoto JM, Heimbach JK, El-Youssef M, Arndt CAS, Rodriguez V, Nageswara Rao AA

Abstract
HCC is rare in the pediatric population, but is the second most common liver malignancy in children. Survival rates for primary unresectable HCC have been dismal. The objective of this study was to describe our experience with a multimodal approach for the management of unresectable HCC in two adolescent patients and to review the literature. Both patients are currently alive with no recurrence at 51 and 29 months post-transplant. Multimodality treatment involving chemotherapy with doxorubicin, cisplatin, and sorafenib; TACE; timely liver transplantation; and post-transplant therapy with sorafenib and mTOR inhibitors may help improve outcomes and prolong survival in pediatric patients with unresectable HCC.

PMID: 28631359 [PubMed - as supplied by publisher]

Transesophageal echocardiography in orthotopic liver transplantation: a comprehensive intraoperative monitoring tool.

Wed, 06/21/2017 - 21:45
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Transesophageal echocardiography in orthotopic liver transplantation: a comprehensive intraoperative monitoring tool.

Crit Ultrasound J. 2017 Dec;9(1):15

Authors: Vetrugno L, Barbariol F, Baccarani U, Forfori F, Volpicelli G, Della Rocca G

Abstract
Intraoperative transesophageal echocardiography is a minimally invasive monitoring tool that can provide real-time visual information on ventricular function and hemodynamic volume status in patients undergoing liver transplantation. The American Association for the Study of Liver Diseases states that transesophageal echocardiography should be used in all liver transplant candidates in order to assess chamber sizes, hypertrophy, systolic and diastolic function, valvular function, and left ventricle outflow tract obstruction. However, intraoperative transesophageal echocardiography can be used to "visualize" other organs too; thanks to its proximity and access to multiple acoustic windows: liver, lung, spleen, and kidney. Although only limited scientific evidence exists promoting this comprehensive use, we describe the feasibility of TEE in the setting of liver transplantation: it is a highly valuable tool, not only as a cardiovascular monitoring, but also as a tool to evaluate lungs and pleural spaces, to assess hepatic vein blood flow and inferior vena cava anastomosis and patency, i.e., in cases of modified surgical techniques. The aim of this case series is to add our own experience of TEE as a comprehensive intraoperative monitoring tool in the field of orthotopic liver transplantation (and major liver resection) to the literature.

PMID: 28631103 [PubMed - in process]

Dermatitis Herpetiformis as the Initial Presentation of Primary Biliary Cholangitis in a Male with Gluten Sensitivity.

Wed, 06/21/2017 - 21:45
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Dermatitis Herpetiformis as the Initial Presentation of Primary Biliary Cholangitis in a Male with Gluten Sensitivity.

Cureus. 2017 May 14;9(5):e1247

Authors: Philips C, Paramaguru R, Indiran DA, Augustine P

Abstract
Celiac disease is commonly associated with elevated liver enzymes that normalize on a gluten-free diet. Celiac disease is rarely described in patients with primary biliary cholangitis. Dermatitis herpetiformis is the skin manifestation of the celiac disease that is very rarely associated with primary biliary cirrhosis. We present the case of a 62-year-old man who presented with severe chronic pruritus, in whom a diagnosis of primary biliary cholangitis was made initially. However, in the presence of atypical skin lesions, not confirming to chronic cholestasis, an in-depth evaluation including histopathological examination led to the diagnosis of dermatitis herpetiformis associated with gluten sensitivity. Gluten-free diet and medical treatment with dapsone led to beneficial clinical outcomes.

PMID: 28630805 [PubMed - in process]

Gut microbiota of liver transplantation recipients.

Wed, 06/21/2017 - 21:45
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Gut microbiota of liver transplantation recipients.

Sci Rep. 2017 Jun 19;7(1):3762

Authors: Sun LY, Yang YS, Qu W, Zhu ZJ, Wei L, Ye ZS, Zhang JR, Sun XY, Zeng ZG

Abstract
The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients with end-stage liver disease. Here, we focused on the characteristics of intestinal fecal microbial communities in post-liver transplantation (LT) patients in comparison with those in the same individuals pre-LT and in healthy individuals. The fecal microbial communities were analyzed via MiSeq-PE250 sequencing of the V4 region of 16S ribosomal RNA and were then compared between groups. We found that the gut microbiota of patients with severe liver disease who were awaiting LT was significantly different from that of healthy controls, as represented by the first principal component (p = 0.0066). Additionally, the second principal component represented a significant difference in the gut microbiota of patients between pre-LT and post-LT surgery (p = 0.03125). After LT, there was a significant decrease in the abundance of certain microbial species, such as Actinobacillus, Escherichia, and Shigella, and a significant increase in the abundance of other microbial species, such as Micromonosporaceae, Desulfobacterales, the Sarcina genus of Eubacteriaceae, and Akkermansia. Based on KEGG profiles, 15 functional modules were enriched and 21 functional modules were less represented in the post-LT samples compared with the pre-LT samples. Our study demonstrates that fecal microbial communities were significantly altered by LT.

PMID: 28630433 [PubMed - in process]

Functional Evaluation of a Bioartificial Liver Support System Using Immobilized Hepatocyte Spheroids in a Porcine Model of Acute Liver Failure.

Wed, 06/21/2017 - 21:45
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Functional Evaluation of a Bioartificial Liver Support System Using Immobilized Hepatocyte Spheroids in a Porcine Model of Acute Liver Failure.

Sci Rep. 2017 Jun 19;7(1):3804

Authors: Lee JH, Lee DH, Lee S, Kwon CHD, Ryu JN, Noh JK, Jang IK, Park HJ, Yoon HH, Park JK, Kim YJ, Kim SK, Lee SK

Abstract
Bioartificial livers (BAL) may offer acute liver failure (ALF) patients an opportunity for cure without liver transplantation. We evaluated the efficacy of a spheroid-based BAL system, containing aggregates of porcine hepatocytes, in a porcine model of ALF. ALF pigs were divided into three groups. The control group consisted of treatment naïve pigs (n = 5), blank group consisted of pigs that were attached to the BAL system not containing hepatocytes for 12 hours (n = 5) and BAL group consisted of pigs that were attached to the BAL containing hepatocytes for 12 hours (n = 5). Increase in serum ammonia levels were significantly greater in the blank group (P < 0.01) and control group (P < 0.01), compared to the BAL group during the treatment period. Increase in ICP was significantly greater in the control group compared to the BAL group (P = 0.01). Survival was significantly prolonged in the BAL group compared to the blank group (P = 0.03). A BAL system with a bioreactor containing hepatocyte spheroids showed effective clearance of serum ammonia, preservation of renal function and delayed ICP increase in a porcine model of ALF.

PMID: 28630420 [PubMed - in process]

Fetal Hypotrophy Is an Important Marker in Diagnosis of Preeclampsia in Pregnant Patients After Solid Organ Transplantation.

Wed, 06/21/2017 - 21:45
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Fetal Hypotrophy Is an Important Marker in Diagnosis of Preeclampsia in Pregnant Patients After Solid Organ Transplantation.

Ann Transplant. 2017 Jun 20;22:370-377

Authors: Cyganek A, Pietrzak B, Dąbrowski FA, Jabiry-Zieniewicz Z, Chlebus M, Wielgos M, Grzechocińska B

Abstract
BACKGROUND The purpose of this study was to use a multidisciplinary approach to define the importance of fetal growth disturbances in pregnant patients after renal or liver transplantation in diagnosis and treatment of preeclampsia. MATERIAL AND METHODS We assessed 108 pregnancies in patients with renal or liver transplants. Statistical analysis included Pearson's chi-square test and Fisher's exact test. RESULTS In the renal transplant (RTR) group, preeclampsia was diagnosed in 40% according to ISSHP. In the liver transplant (LTR) group, ISSHP guidelines allow this diagnose in 14.6% of patients. Intrauterine fetal hypotrophy occurred in 53.3% of RTR patients with clinical symptoms of preeclampsia and in none of stabile patients. Premature delivery rate was 40% in patients with hypotrophy and only in 15.5% without. For LTR patients, hypotrophy was diagnosed in 16.4% patients with clinical symptoms of preeclampsia and in 12.7% of stabile patients. Premature delivery rate was 14.5% in patients with hypotrophy and in 14.5% without. CONCLUSIONS Fetal hypotrophy is strongly associated with premature delivery and risk of preeclampsia in pregnancies after renal transplantation. There is a need for including ultrasound findings in diagnostic criteria of preeclampsia. Fetal growth monitoring may help in prediction of premature delivery in these group.

PMID: 28630397 [PubMed - in process]

Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity.

Wed, 06/21/2017 - 21:45
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Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity.

Proc Natl Acad Sci U S A. 2017 Jun 19;:

Authors: Cao D, Cao QM, Subramaniam S, Yugo DM, Heffron CL, Rogers AJ, Kenney SP, Tian D, Matzinger SR, Overend C, Catanzaro N, LeRoith T, Wang H, Piñeyro P, Lindstrom N, Clark-Deener S, Yuan L, Meng XJ

Abstract
Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ-specific CD4(+) T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α-specific CD8(+) T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E.

PMID: 28630341 [PubMed - as supplied by publisher]

Acute pneumatosis cystoides intestinalis with atrophic desmosis of the colon in a child.

Wed, 06/21/2017 - 21:45
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Acute pneumatosis cystoides intestinalis with atrophic desmosis of the colon in a child.

BMJ Case Rep. 2017 Jun 19;2017:

Authors: Schuster B, Mayr J

Abstract
Acute pneumatosis cystoides intestinalis (PCI) has been described after bone marrow transplantation (BMT). Several case series have demonstrated successful conservative treatment of PCI in children. We present a child with Fanconi anaemia, who developed severe graft versus host disease of the gastrointestinal tract, skin and liver after BMT and an acute, severe form of PCI. Our case report illustrates the complexity of diagnostic and therapeutic procedures in PCI in immunocompromised children.

PMID: 28630222 [PubMed - in process]

Prognostic nomogram for patients with non-B non-C hepatocellular carcinoma after curative liver resection.

Wed, 06/21/2017 - 21:45
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Prognostic nomogram for patients with non-B non-C hepatocellular carcinoma after curative liver resection.

Int J Surg. 2017 Jun 16;:

Authors: Zhang W, Tan Y, Jiang L, Yan L, Yang J, Li B, Wen T, Wu H, Wang W, Xu M

Abstract
BACKGROUND: The proportion of the both serum hepatitis B surface antigen and hepatitis C antibody negative hepatocellular carcinoma (NBNC HCC) patients are tended to increase recently. We investigated the characteristics and surgical outcome for those patients after liver resection.
METHODS: Four hundred and thirty-five NBNC patients were involved in our study. According to the results of the HBcAb in the serum, those patients were divided into HBcAb-positive subgroup (n=328) and HBcAb-negative subgroup (n=107). Based on the multivariate risk factors, the nomogram was constructed for predicting the possibility for over survival (OS) rate.
RESULTS: For all of the NBNC HCC patients, the median OS was 57 months with 5-year OS rate 54.0%. The positive HBcAb NBNC patients were associating with a better liver function (p=0.026), higher AFP (p<0.001) and more proportion of micro-vascular invasion (p=0.001). Multivariate analysis revealed that worse liver function (Child-Pugh B, HR=1.93; 95% CI: 1.23 - 3.04), vascular invasion (MIVI vs negative, HR=1.86; 95% CI: 1.21 - 2.86, MAVI vs negative, HR=2.05; 95% CI: 1.37 - 3.06), poorer ES differentiation (HR=2.34; 95% CI: 1.67 - 3.30) and larger tumor size (HR=1.10; 95% CI: 1.06 - 1.15) were associated with the worse OS.
CONCLUSION: we established a novel prognostic nomogram to predict the OS of NBNC HCC patients after liver resection. The prognosis of NBNC HCC was mainly determined by tumor stage and liver function not by the previous etiologies.

PMID: 28629767 [PubMed - as supplied by publisher]

Delayed referral to specialist centre increases morbidity in patients with bile duct injury (BDI) after laparoscopic cholecystectomy (LC).

Wed, 06/21/2017 - 21:45
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Delayed referral to specialist centre increases morbidity in patients with bile duct injury (BDI) after laparoscopic cholecystectomy (LC).

Int J Surg. 2017 Jun 16;:

Authors: Martinez-Lopez S, Upasani V, Pandanaboyana S, Attia M, Toogood G, Lodge P, Hidalgo E

Abstract
BACKGROUND: There is still a debate regarding the optimal management of bile duct injury following cholecystectomy. Our aim was to ascertain if delayed referral influenced clinical outcomes for patients with BDI treated in our institution.
MATERIALS AND METHODS: We interrogated a prospectively maintained database, including all patients with BDI (Bismuth and Strasberg classifications) post LC managed in our unit from 2000-2014. Referrals were arbitrarily defined as early (<96 hours from the injury) and delayed (>96 hours).
RESULTS: 68 patients with BDI were managed. Patient demographics, referral time, level of injury and morbidity data was collected. 50 patients (77%) required a surgical bile duct reconstruction. The Early referral Group included 33 patients (52.4%) and Delayed referral group 30 (47.6%). The patients referred late had a significantly high incidence of right hepatic artery injury (23% vs. 3%) and the overall number of complications (0.0001). The average number of surgical interventions (2.5 vs 1.8, p<0.05) and invasive procedures (4 vs. 2.5, p< 0.05) per patient was high in the late referral group. There was significant difference in the interval between BDI-to-reconstruction (median 3 vs. median 88 days, p< 0.05) and referral-to-hospital discharge (median 9 vs. median days 59, p< 0.05). On multivariate analysis only delayed referral (OR 7.58, 95% CI 2.1-26.6) and Strasberg-E injuries (OR 4.86, 95% CI 1.1-20.9) were significant.
CONCLUSION: A late referral was associated with a higher incidence of post-treatment complications, greater need for invasive procedures and a longer recovery period. These observations support the need for early patient transfer to a tertiary institution following BDI.

PMID: 28629763 [PubMed - as supplied by publisher]

Positron emission tomography/computed tomography in patients with hepatocellular carcinoma undergoing liver transplantation. Useful, necessary or irrelevant?

Wed, 06/21/2017 - 21:45
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Positron emission tomography/computed tomography in patients with hepatocellular carcinoma undergoing liver transplantation. Useful, necessary or irrelevant?

Eur J Radiol. 2017 Jun;91:155-159

Authors: Cascales-Campos PA, Romero PR, Schneider MA, Lopez-Lopez V, Navarro JL, Frutos L, Pons Miñano JA, Paricio PP

Abstract
Hepatocellular Carcinoma (HCC) is an aggressive tumor entity, with the only curative options being surgical resection or orthotopic liver transplantation (OLT). The presence of one single tumor nodule of less than 5 centimeters diameter or a maximum of 3 nodules, with the largest of these not exceeding 3 centimeters (Milan criteria) constitute the clinical situation in which the best results for OLT in patients with HCC have been achieved. The survival of patients fulfilling the Milan criteria after transplantation is comparable to patients with similar tumor stages without cirrhosis, undergoing hepatic resection. The application of PET in oncology has become increasingly common in the last decade as it is a non-invasive tool that also gathers information about the degree of the biological aggressiveness of the tumor. The objective of this study was to perform a review of the literature, identifying the strengths and weaknesses of the PET as a prognostic tool in patients with HCC after OLT.

PMID: 28629563 [PubMed - in process]

Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review.

Wed, 06/21/2017 - 21:45
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Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review.

Ann Intern Med. 2017 May 02;166(9):637-648

Authors: Falade-Nwulia O, Suarez-Cuervo C, Nelson DR, Fried MW, Segal JB, Sulkowski MS

Abstract
Background: Rapid improvements in hepatitis C virus (HCV) therapy have led to the approval of multiple oral direct-acting antiviral (DAA) regimens by the U.S. Food and Drug Administration (FDA) for treatment of chronic HCV infection.
Purpose: To summarize published literature on the efficacy and safety of oral DAAs for treatment of persons with chronic HCV infection.
Data Sources: MEDLINE and EMBASE from inception through 1 November 2016.
Study Selection: 42 English-language studies from controlled and single-group registered clinical trials of adults with HCV infection that evaluated at least 8 weeks of an FDA-approved interferon-free HCV regimen that included at least 2 DAAs.
Data Extraction: Two investigators abstracted data on study design, patient characteristics, and virologic and safety outcomes sequentially and assessed quality independently.
Data Synthesis: Six DAA regimens showed high sustained virologic response (SVR) rates (>95%) in patients with HCV genotype 1 infection without cirrhosis, including those with HIV co-infection. Effective treatments for HCV genotype 3 infection are limited (2 DAA regimens). Patients with hepatic decompensation, particularly those with Child-Turcotte-Pugh class C disease, had lower SVR rates (78% to 87%) than other populations. The addition of ribavirin was associated with increased SVR rates for certain DAA regimens and patient groups. Overall rates of serious adverse events and treatment discontinuation were low (<10% in the general population); regimens that included ribavirin had more mild or moderate adverse events than those without.
Limitations: Twenty-three studies had moderate risk of bias (10 were open-label single-group trials, 11 had limited information on concealment of the allocation scheme, and 5 had selective outcome reporting). All but 1 of the studies were industry-funded. Heterogeneity of interventions precluded pooling.
Conclusion: Multiple oral DAA regimens show high rates of safety, tolerability, and efficacy for treatment of HCV genotype 1 infection, particularly among persons without cirrhosis.
Primary Funding Source: Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42014009711).

PMID: 28319996 [PubMed - indexed for MEDLINE]

Hyponatremia - unfavourable prognostic factor in hepatic cirrhosis.

Wed, 06/21/2017 - 21:45
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Hyponatremia - unfavourable prognostic factor in hepatic cirrhosis.

Rom J Intern Med. 2016 Dec 01;54(4):207-210

Authors: Enescu A, Petrescu F, Mitruţ P, Pădureanu V, Petrescu OI, Albu VC, Moraru AL, Enescu AŞ

Abstract
Hyponatremia is defined by a level of Na in serum below or equal to 136 mEq/L while in hepatic cirrhosis it is classically considered as relevant only at a level of Na below 130 mEq/L. Hyponatremia frequently occurs in patients with end-stage hepatic disease. The frequency and severity are variable but it has been estimated that it occurs with a frequency of 57% in hospitalized patients with cirrhosis and in those on waiting lists for hepatic transplants. Signs and symptoms of hyponatremia are related to dysfunctions of the central nervous system, due to migration of the water from intravascular space to the brain cells, resulting in the occurrence of cerebral edema. Therapeutic options in hyponatremia are limited and are based on restriction of water consumption, exclusion of diuretics and vaptans. Hepatic transplant remains the only definitive treatment for end-stage hepatic diseases in which hyponatremia has occurred.

PMID: 28002032 [PubMed - indexed for MEDLINE]

Diet Polyphenol Curcumin Stimulates Hepatic Fgf21 Production and Restores Its Sensitivity in High-Fat-Diet-Fed Male Mice.

Wed, 06/21/2017 - 21:45
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Diet Polyphenol Curcumin Stimulates Hepatic Fgf21 Production and Restores Its Sensitivity in High-Fat-Diet-Fed Male Mice.

Endocrinology. 2017 Feb 01;158(2):277-292

Authors: Zeng K, Tian L, Patel R, Shao W, Song Z, Liu L, Manuel J, Ma X, McGilvray I, Cummins CL, Weng J, Jin T

Abstract
We found previously that short-term curcumin gavage stimulated mouse hepatic fibroblast growth factor 21 (Fgf21) expression. Here we conducted mechanistic exploration and investigated the potential pathophysiological relevance on this regulation. Fgf21 stimulation was observed at messenger RNA and protein levels in mice with daily curcumin gavage for 4 or 8 days and in primary hepatocytes with curcumin treatment. Using peroxisome proliferator-activated receptor α (PPARα) agonist and antagonist, along with luciferase reporter and chromatin immune-precipitation approaches, we determined that curcumin stimulates Fgf21 transcription in a mechanism involving PPARα activation. High-fat diet (HFD) feeding also increased mouse hepatic and serum Fgf21 levels, whereas dietary curcumin intervention attenuated these increases. We found that HFD feeding reduced hepatic expression levels of genes that encode FGFR1 and βKlotho, PGC1α, and the targets of the PPARα-PGC1α axis, whereas concomitant curcumin intervention restored or partially restored their expression levels. Importantly, hepatocytes from HFD-fed mice showed a loss of response to FGF21 treatment on Erk phosphorylation and the expression of Egr1 and cFos; this response was restored in hepatocytes from HFD-fed mice with curcumin intervention. This investigation expanded our mechanistic understanding of the metabolic beneficial effects of dietary curcumin intervention involving the regulation of Fgf21 production and the attenuation of HFD-induced Fgf21 resistance.

PMID: 27967217 [PubMed - indexed for MEDLINE]

Role of liver-directed local tumor therapy in the management of hepatocellular carcinoma with extrahepatic metastases: a SEER database analysis.

Wed, 06/21/2017 - 21:45
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Role of liver-directed local tumor therapy in the management of hepatocellular carcinoma with extrahepatic metastases: a SEER database analysis.

Expert Rev Gastroenterol Hepatol. 2017 Feb;11(2):183-189

Authors: Abdel-Rahman O

Abstract
BACKGROUND: This study assessed the prognostic impact of the liver-directed local tumor therapy in the management of hepatocellular carcinoma (HCC) with extrahepatic metastases.
METHODS: Metastatic HCC patients diagnosed between 2004 and 2013 were identified from the SEER (Surveillance, Epidemiology, and End Results) database. Propensity-matched analysis was performed considering baseline characteristics (age, gender, race, histology, TNM stage, site of metastases, fibrosis score and alpha fetoprotein).
RESULTS: A total of 2529 patients were identified. The median age was 65 years, and 151 patients received liver-directed local treatment (either surgical treatment or local destructive treatment). Both before and after propensity score matching, cancer-specific and overall survival (p < 0.0001 for all) were better in the liver-directed local therapy group. When the overall survival was stratified by the type of local treatment (surgical resection versus destructive treatment), both types of treatment improved overall survival (p < 0.0001 for both). In multivariate analysis of the matched population, the only factor correlated with better survival receiving is local therapy (p < 0.0001).
CONCLUSION: This analysis suggests that liver-directed local treatment may play a role -in addition to systemic treatment- in the management of selected patients with metastatic HCC. Further prospective randomized controlled trials are needed to confirm or deny this hypothesis.

PMID: 27830958 [PubMed - indexed for MEDLINE]

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