Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 38
Filter
1.
Transplant Direct ; 10(7): e1663, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38953038

ABSTRACT

Background: Enhanced recovery after surgery (ERAS) pathways represent a comprehensive approach to optimizing perioperative management and reducing hospital stay and cost. In living donor kidney transplantation, key impediments to postoperative discharge include pain, and opioid associated complications such as nausea, vomiting, and the return of gastrointestinal function. Methods: In this randomized controlled trial, living kidney transplantation donors were assigned to either the ERAS or control group. The ERAS group patients received 15 preoperative, 17 intraoperative, 19 postoperative element intervention. The control group received standard care. The ERAS group received a multimodal opioid sparing pain management including an intraoperative transverse abdominis plane block. Our primary outcome measure was postoperative opioid consumption. The secondary outcome measures were postoperative pain scores, first oral intake, and hospital length of stay. Results: There were no significant differences in demographics between the 2 groups. The ERAS group had a statistically significant reduction in total postoperative opioid consumption calculated in intravenous morphine equivalents (24.2 ±â€…20.2 versus 71 ±â€…39.5 mg, P < 0.01). Postoperative pain scores were significantly lower (P < 0.001) from 1 h postoperatively to 48 h. Surgical time was 45 min shorter (P = 0.037). Intraoperative PlasmaLyte administration was lower (PlasmaLyte: 1444 ±â€…907 versus 2168 ±â€…1347 mL, P = 0.049). Time to tolerating regular diet was shorter by 2 h (P < 0.008), and length of hospital stay was decreased by 10.1 h. Conclusions: The ERAS group experienced superior postoperative analgesia and a shorter length of hospital stay compared with controls.

2.
World J Oncol ; 15(3): 511-520, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38751709

ABSTRACT

Hepatocellular carcinoma (HCC) is often diagnosed at a late stage and frequently recurs despite curative intervention, leading to poor survival outcomes. Frontline systemic therapies include combination immunotherapy regimens and tyrosine kinase inhibitors. We report a case of a 38-year-old woman with chronic hepatitis B and C coinfection-associated non-cirrhotic HCC, which recurred in the peritoneum after initial resection of her primary tumor. Disease progression occurred on both atezolizumab/bevacizumab and lenvatinib, and she was subsequently treated with gemcitabine and oxaliplatin (GEMOX) chemotherapy and exhibited a profound clinical response on imaging with normalization of alpha fetoprotein (AFP) after several months. Following extensive multidisciplinary discussion, she underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) that removed all visible macroscopic tumor. Her pathology demonstrated a complete pathologic response. She received two additional months of postoperative chemotherapy, and then proceeded with close monitoring off therapy. To our knowledge, this is the first reported case of a complete pathologic response to GEMOX chemotherapy in the context of CRS/HIPEC for peritoneal metastases in HCC, after progression on standard immunotherapy and tyrosine kinase inhibitor treatments. In this report, we review the current systemic treatment landscape in HCC. We highlight potential consideration of cytotoxic chemotherapy, which is less frequently utilized in current practice, in selected patients with HCC, and discuss the role of CRS/HIPEC in the management of peritoneal metastases. Further investigation regarding predictors of response to systemic treatments is strongly needed. Multidisciplinary management may ultimately prolong survival in patients with advanced HCC.

3.
BMC Genomics ; 25(1): 437, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698335

ABSTRACT

BACKGROUND: Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation). RESULTS: We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, suggesting acceptability from a molecular standpoint. Liver metabolic functional genes were similarly upregulated, and extracellular matrix genes were similarly downregulated in the accepted and rejected-2 groups compared to rejected-1. The transcriptomic pattern of the rejected-2 subset was enriched for a gene expression signature of graft success post-transplantation. Serum AST, ALT, and total bilirubin levels showed similar overlapping patterns. Additional histopathological filtering identified cases with borderline scores and extensive molecular overlap with accepted donor livers. CONCLUSIONS: Our integrated approach identified a subset of rejected donor livers that are likely suitable for transplantation, demonstrating the potential to expand the pool of transplantable livers.


Subject(s)
Gene Expression Profiling , Liver Transplantation , Liver , Tissue Donors , Humans , Liver/metabolism , Liver/pathology , Male , Middle Aged , Female , Transcriptome , Graft Rejection/genetics , Adult
4.
Am J Transplant ; 24(4): 619-630, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37940005

ABSTRACT

The recent shortage of the University of Wisconsin (UW) solution prompted increased utilization of histidine-tryptophan-ketoglutarate (HTK) solution for liver graft preservation. This contemporary study analyzed deceased donor liver transplant outcomes following preservation with HTK vs UW. Patients receiving deceased donor liver transplantations between January 1, 2019, and June 30, 2022, were retrospectively identified utilizing the Organ Procurement and Transplant Network database, stratified by preservation with HTK vs UW, and a propensity score matching analysis was performed. Outcomes assessed included rates of primary nonfunction, graft survival, and patient survival. There were 4447 patients in each cohort. Primary nonfunction occurred in 60 (1.35%) patients in the HTK group vs 25 (0.54%) in the UW group (P < .001). HTK was associated with lower 90-day graft survival (94.39% vs 96.09%; P < .001) and 90-day patient survival (95.97% vs 97.38%; P = .001). Unmatched donation after cardiac death-specific analysis of HTK vs UW demonstrated respective rates of primary nonfunction of 1.63% vs 0.82% (P = .20), 90-day graft survival of 92.50% vs 95.29% (P = .069), and 90-day patient survival of 93.90% vs 96.35% (P = .077). These results suggest that HTK may not be an equivalent preservation solution for deceased donor liver transplantation.


Subject(s)
Liver Transplantation , Organ Preservation Solutions , Humans , Retrospective Studies , Propensity Score , Living Donors , Glucose , Mannitol , Potassium Chloride , Procaine , Insulin , Glutathione , Allopurinol
5.
N Engl J Med ; 389(21): 1972-1978, 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-37991855

ABSTRACT

Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.


Subject(s)
Genetic Diseases, Inborn , Glucagon , Hypertension, Portal , Liver Transplantation , Female , Humans , Esophageal and Gastric Varices/etiology , Esophageal and Gastric Varices/surgery , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/surgery , Glucagon/blood , Glucagon/genetics , Hypertension, Portal/blood , Hypertension, Portal/etiology , Hypertension, Portal/genetics , Hypertension, Portal/surgery , Hypertrophy/genetics , Liver Cirrhosis , Genetic Diseases, Inborn/blood , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/surgery , Pancreatic Diseases/genetics , Pancreatic Diseases/pathology , Pancreatic Diseases/surgery , Glucagon-Secreting Cells/pathology
6.
Transplant Direct ; 9(11): e1521, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37829245

ABSTRACT

Background: Organ donors supported by extracorporeal membrane oxygenation (ECMO) have historically been considered high-risk and are judiciously utilized. This study examines transplant outcomes using renal allografts from donors supported on ECMO for nondonation purposes. Methods: Retrospective review of the Gift of Life (Pennsylvania, New Jersey, Delaware) organ procurement organization database, cross-referenced to the Organ Procurement and Transplantation Network database, assessed kidney transplants using donors supported on venoarterial (VA) and venovenous (VV) ECMO for nondonation purposes. Transplants using VA- and VV-ECMO donors were compared with Kidney Donor Profile Index (KDPI)-stratified non-ECMO donors. Regression modeling of the entire ECMO and non-ECMO populations assessed ECMO as predictive of graft survival. Additional regression of the ECMO population alone assessed for donor features associated with graft survival. Results: Seventy-eight ECMO donors yielded 128 kidney transplants (VA: 80, VV: 48). Comparing outcomes using these donors to kidney transplants using organs from KDPI-stratified non-ECMO donors, VA- and VV-ECMO donor grafts conferred similar rates of delayed graft function and posttransplant renal function to KDPI-matched non-ECMO counterparts. VA-ECMO kidneys demonstrated superior graft survival compared with the lowest-quality (KDPI 86%-100%) non-ECMO kidneys and similar graft survival to KDPI <85% non-ECMO kidneys. VV-ECMO showed inferior graft survival to all but the lowest-quality (KDPI 86%-100%) non-ECMO kidneys. VV-ECMO, but not VA-ECMO, was associated with increased risk of graft loss on multivariable regression (hazard ratios-VA: 1.02, VV: 2.18). Higher KDPI, advanced age, increased body mass index, hypertension, and diabetes were identified as high-risk features of ECMO donors. Conclusions: Kidney transplantation using appropriately selected ECMO donors can safely expand the donor pool. Ongoing studies are necessary to determine best practice patterns using kidneys from these donors.

7.
Liver Transpl ; 29(11): 1151-1160, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37387680

ABSTRACT

Liver transplantation continues to face significant organ shortages and efficient utilization of marginal donors is paramount. This study evaluates the practice patterns and outcomes in liver transplantation when utilizing allografts from marginal donors who required extracorporeal membrane oxygenation (ECMO) support. We performed a retrospective review of the Gift of Life (PA, NJ, DE) organ-procuring organization database for transplants performed using donors supported on ECMO for nondonation purposes. These were cross-referenced to the transplant recipients within the Organ Procurement and Transplantation Network database, and the outcomes of liver transplants using donors on ECMO support were compared with those not requiring ECMO. Organ use and nonuse patterns were then evaluated in ECMO-supported donors, identifying the factors associated with nonuse compared with the factors associated with graft failure. Thirty-nine of the 84 ECMO-supported donors contributing at least one intra-abdominal organ for transplant donated a liver. Graft survival and patient survival up to 5 years were comparable between transplants from ECMO and non-ECMO-supported donors, and no cases of primary nonfunction were seen in the ECMO group. ECMO support was not associated with 1-year graft failure on regression modeling. Additional regression analyses within the ECMO donor population identified bacteremia (HR: 19.81) and elevated total bilirubin at donation (HR: 2.44) as predictive of post-transplant graft failure. Livers from donors supported on ECMO before donation appear safe to use in select transplant settings. Better understanding of the impact of predonation ECMO on liver allograft function will help guide the optimal use of these scarcely used donors.


Subject(s)
Extracorporeal Membrane Oxygenation , Liver Transplantation , Tissue and Organ Procurement , Humans , Liver Transplantation/adverse effects , Extracorporeal Membrane Oxygenation/adverse effects , Tissue Donors , Transplantation, Homologous , Graft Survival , Retrospective Studies
8.
Liver Transpl ; 29(11): 1172-1180, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37379011

ABSTRACT

Sex and racial disparities in deceased donor liver transplantation (DDLT) have been described, but this has not been well studied in living donor liver transplantation (LDLT). We aim to examine these disparities in the US LDLT population and identify potential predictors of these differences. From 2002 to 2021, the Organ Procurement and Transplant Network database was queried to characterize the adult LDLT population and evaluate differences between LDLT and DDLT recipients with regard to sex and race. Donor demographics, Model for End-stage Liver Disease (MELD), and socioeconomic data were all included. Of the 4961 LDLT and 99,984 DDLT recipients, males received the majority of LDLT (55% vs. 45%, p < 0.001) and DDLT (67% vs. 33%, p < 0.001) compared to females. There was a significant difference in race between male and female LDLT recipients ( p < 0.001); 84% of male recipients were White and 78% of females. In both groups, females had lower levels of education and were less likely to have private insurance. There were more female living donors (N = 2545, 51%); 50% of female donors donated to males but only 40% of males donated to females. Donor-recipient relationships varied significantly by sex ( p < 0.001); males received more donations from spouses (62% vs. 39%) and siblings (60% vs. 40%). In the LDLT population, significant disparities exist with respect to sex and race that disadvantage women, but these disparities are less pronounced than in the DDLT population. Although further studies are needed, complex clinical and socioeconomic differences as well as donor factors may explain these variations.


Subject(s)
End Stage Liver Disease , Liver Transplantation , Adult , Humans , Male , Female , United States/epidemiology , Living Donors , Liver Transplantation/adverse effects , Liver Transplantation/methods , End Stage Liver Disease/surgery , Retrospective Studies , Severity of Illness Index , Treatment Outcome
9.
Neuromodulation ; 26(2): 320-332, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35219571

ABSTRACT

BACKGROUND: Deep brain stimulation (DBS) programming of multicontact DBS leads relies on a very time-consuming manual screening procedure, and strategies to speed up this process are needed. Beta activity in subthalamic nucleus (STN) local field potentials (LFP) has been suggested as a promising marker to index optimal stimulation contacts in patients with Parkinson disease. OBJECTIVE: In this study, we investigate the advantage of algorithmic selection and combination of multiple resting and movement state features from STN LFPs and imaging markers to predict three relevant clinical DBS parameters (clinical efficacy, therapeutic window, side-effect threshold). MATERIALS AND METHODS: STN LFPs were recorded at rest and during voluntary movements from multicontact DBS leads in 27 hemispheres. Resting- and movement-state features from multiple frequency bands (alpha, low beta, high beta, gamma, fast gamma, high frequency oscillations [HFO]) were used to predict the clinical outcome parameters. Subanalyses included an anatomical stimulation sweet spot as an additional feature. RESULTS: Both resting- and movement-state features contributed to the prediction, with resting (fast) gamma activity, resting/movement-modulated beta activity, and movement-modulated HFO being most predictive. With the proposed algorithm, the best stimulation contact for the three clinical outcome parameters can be identified with a probability of almost 90% after considering half of the DBS lead contacts, and it outperforms the use of beta activity as single marker. The combination of electrophysiological and imaging markers can further improve the prediction. CONCLUSION: LFP-guided DBS programming based on algorithmic selection and combination of multiple electrophysiological and imaging markers can be an efficient approach to improve the clinical routine and outcome of DBS patients.


Subject(s)
Deep Brain Stimulation , Parkinson Disease , Subthalamic Nucleus , Humans , Deep Brain Stimulation/methods , Movement/physiology , Parkinson Disease/diagnostic imaging , Parkinson Disease/therapy , Subthalamic Nucleus/diagnostic imaging , Subthalamic Nucleus/physiology , Treatment Outcome , Biomarkers
10.
Transpl Int ; 35: 10175, 2022.
Article in English | MEDLINE | ID: mdl-35865863

ABSTRACT

Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) has become the second leading cause of HCC-related liver transplantation in the United States. This study investigated post-transplant recurrence and survival for patients transplanted for NASH-related HCC compared to non-NASH HCC etiologies. Retrospective review of the United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN) database identified 7,461 patients with HCC-1,405 with underlying NASH and 6,086 with non-NASH underlying diseases. After propensity score matching (PSM) to account for patient- and tumor-related confounders 1,175 remained in each group. Primary outcomes assessed were recurrence rate and recurrence-free survival. Recurrent malignancy at 5 years post-transplant was lower in NASH compared to non-NASH patients (5.80 vs. 9.41%, p = 0.01). Recurrence-free survival, however, was similar at 5 years between groups. Patients with NASH-related HCC were less likely to have post-transplant recurrence than their non-NASH counterparts, although recurrence-free survival was similar at 5 years.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/surgery , Humans , Liver Neoplasms/surgery , Neoplasm Recurrence, Local , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/surgery , Propensity Score , Retrospective Studies , Risk Factors , United States
11.
Liver Transpl ; 28(4): 623-635, 2022 04.
Article in English | MEDLINE | ID: mdl-34564931

ABSTRACT

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) affects both recipient and donor populations in liver transplantation. Presently, it is unclear whether transplantation of macrosteatotic allografts is affected by the metabolic milieu of liver transplant recipients. This study investigates fatty liver disease at the intersection of donor and recipient. A retrospective review of the Organ Procurement and Transplantation database identified 5167 NASH and 26,289 non-NASH transplant recipients who received transplants from January 1, 2004, to June 12, 2020. A total of 12,569 donors had allografts with no macrosteatosis (<5%), 16,140 had mild macrosteatosis (5%-29%), and 2747 had moderate to severe macrosteatosis (≥30%). Comparing recipients with NASH to propensity score-matched (PSM) recipients without NASH demonstrated noninferior graft and patient survival up to 10 years in patients with NASH. Similar trends were observed in subgroup analyses of transplants within each strata of allograft macrosteatosis. Assessing allograft macrosteatosis specifically in the NASH population demonstrated that allografts with ≥30% macrosteatosis were associated with reduced early graft survival (30 days, 93.32% versus 96.54% [P = 0.02]; 1 year, 84.53% versus 88.99% [P = 0.05]) compared with PSM grafts with <30% macrosteatosis. Long-term graft survival at 5 and 10 years, however, was similar. The use of carefully selected macrosteatotic allografts can be successful in both recipients with NASH and recipients without NASH. The metabolic environment of patients with NASH does not appear to adversely affect outcomes with regard to the allograft when controlled for numerous confounders. It is, however, important to remain cognizant of the potential for high-risk macrosteatotic allografts to negatively affect outcomes.


Subject(s)
Liver Transplantation , Non-alcoholic Fatty Liver Disease , Allografts , Graft Survival , Humans , Liver Transplantation/adverse effects , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/surgery , Retrospective Studies , Tissue Donors , Treatment Outcome
13.
Transpl Int ; 34(6): 1052-1064, 2021 06.
Article in English | MEDLINE | ID: mdl-33884677

ABSTRACT

Rates of simultaneous liver kidney (SLK) transplantation in the United States have progressively risen. On 8/10/17, the Organ Procurement and Transplantation Network implemented a policy defining criteria for SLK, with a "Safety Net" to prioritize kidney allocation to liver recipients with ongoing renal failure. We performed a retrospective review of the United Network for Organ Sharing (UNOS) database to evaluate policy impact on SLK, kidney after liver (KAL) and kidney transplant alone (KTA). Rates and outcomes of SLK and KAL transplants were compared, as was utilization of high-quality kidney allografts with Kidney Donor Profile Indices (KDPI) <35%. Here, SLK transplants comprised 9.0% and 4.5% of total postpolicy liver and kidney transplants compared to 10.2% and 5.5% prior. Policy enactment did not affect 1-year graft or patient survival for SLK and KAL populations. Less postpolicy SLK transplants utilized high-quality kidney allografts; in all transplant settings, outcomes using high-quality grafts remained stable. These findings suggest that policy implementation has reduced kidney allograft use in SLK transplantation, although both SLK and KAL rates have recently increased. Despite decreased high-quality kidney allograft use, SLK and KAL outcomes have remained stable. Additional studies and long-term follow-up will ensure optimal organ access and sharing.


Subject(s)
Tissue and Organ Procurement , Graft Survival , Humans , Kidney , Liver , Policy , Retrospective Studies , Risk Factors , United States
14.
Case Rep Transplant ; 2021: 5159934, 2021.
Article in English | MEDLINE | ID: mdl-34987880

ABSTRACT

INTRODUCTION: Hepatitis A infection (HAV) is generally characterized by an acute icteric illness or may have a subclinical self-limited course, although rarely, can result in fulminant hepatitis and death. In 2019, the City of Philadelphia declared a public health emergency due to an HAV outbreak. We are reporting a series of four cases of acute liver failure (ALF) requiring liver transplantation (LT) due to acute HAV. METHODS: Chart review and case descriptions of four patients with acute HAV-related ALF who were expeditiously evaluated, listed as Status 1A, and who underwent LT between August 2019 and October 2019 at Thomas Jefferson University Hospital. RESULTS: All four patients presented with acute hepatocellular jaundice and had a positive HAV IgM, and all other causes of ALF were excluded. All four cases met the American Association for the Study of Liver Diseases (AASLD) criteria for ALF. Three of the four cases met King's College Criteria of poor prognosis for nonacetaminophen-induced ALF. All four patients underwent successful LT and were discharged six to twelve days postoperatively. One patient died of disseminated Aspergillus infection five months after LT, while the others have had excellent clinical outcomes shown by one-year follow-ups. All four explants had remarkably similar histological changes, revealing acute hepatitis with massive necrosis accompanied by a prominent lymphoplasmacytic inflammatory infiltrate and bile ductular proliferation. CONCLUSION: Although rare, patients presenting with acute HAV need close monitoring as they may rapidly progress to ALF. Early referral to a transplant center afforded timely access to LT and yielded overall good one-year survival. Widespread HAV vaccination for high-risk individuals is an essential strategy for preventing disease and curbing such future outbreaks.

15.
Int J Mol Sci ; 21(18)2020 Sep 15.
Article in English | MEDLINE | ID: mdl-32942580

ABSTRACT

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality worldwide. Most patients are diagnosed with advanced disease, limiting their options for treatment. While current treatments are adequate for lower staged disease, available systemic treatments are limited, with marginal benefit at best. Chimeric antigen receptor (CAR) T cell therapy, effective in treating liquid tumors such as B-cell lymphoma, presents a potentially promising treatment option for advanced HCC. However, new challenges specific to solid tumors, such as tumor immunoanatomy or the immune cell presence and position anatomically and the tumor microenvironment, need to be defined and overcome. Immunotherapy currently in use must be re-engineered and re-envisioned to treat HCC with the hopes of ushering in an answer to advanced stage solid tumor disease processes. Future therapy options must address the uniqueness of the tumors under the umbrella of HCC. This review strives to summarize HCC, its staging system, current therapy and immunotherapy medications currently being utilized or studied in the treatment of HCC with the hopes of highlighting what is being done and suggesting what needs to be done in the future to champion this therapy as an effective option.


Subject(s)
Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/immunology , Liver Neoplasms/therapy , B-Lymphocytes/immunology , Humans , Immunotherapy/methods , T-Lymphocytes/immunology , Tumor Microenvironment/immunology
16.
Front Cell Dev Biol ; 8: 709, 2020.
Article in English | MEDLINE | ID: mdl-32850829

ABSTRACT

Hepatic stellate cells (HSCs) are a significant component of the hepatocellular carcinoma (HCC) tumor microenvironment (TME). Activated HSCs transform into myofibroblast-like cells to promote fibrosis in response to liver injury or chronic inflammation, leading to cirrhosis and HCC. The hepatic TME is comprised of cellular components, including activated HSCs, tumor-associated macrophages, endothelial cells, immune cells, and non-cellular components, such as growth factors, proteolytic enzymes and their inhibitors, and other extracellular matrix (ECM) proteins. Interactions between HCC cells and their microenvironment have become topics under active investigation. These interactions within the hepatic TME have the potential to drive carcinogenesis and create challenges in generating effective therapies. Current studies reveal potential mechanisms through which activated HSCs drive hepatocarcinogenesis utilizing matricellular proteins and paracrine crosstalk within the TME. Since activated HSCs are primary secretors of ECM proteins during liver injury and inflammation, they help promote fibrogenesis, infiltrate the HCC stroma, and contribute to HCC development. In this review, we examine several recent studies revealing the roles of HSCs and their clinical implications in the development of fibrosis and cirrhosis within the hepatic TME.

17.
Neuroimage Clin ; 27: 102271, 2020.
Article in English | MEDLINE | ID: mdl-32446242

ABSTRACT

Deep brain stimulation (DBS) therapy requires extensive patient-specific planning prior to implantation to achieve optimal clinical outcomes. Collective analysis of patient's brain images is promising in order to provide more systematic planning assistance. In this paper the design of a normalization pipeline using a group specific multi-modality iterative template creation process is presented. The focus was to compare the performance of a selection of freely available registration tools and select the best combination. The workflow was applied on 19 DBS patients with T1 and WAIR modality images available. Non-linear registrations were computed with ANTS, FNIRT and DRAMMS, using several settings from the literature. Registration accuracy was measured using single-expert labels of thalamic and subthalamic structures and their agreement across the group. The best performance was provided by ANTS using the High Variance settings published elsewhere. Neither FNIRT nor DRAMMS reached the level of performance of ANTS. The resulting normalized definition of anatomical structures were used to propose an atlas of the diencephalon region defining 58 structures using data from 19 patients.


Subject(s)
Brain/diagnostic imaging , Brain/physiopathology , Deep Brain Stimulation , Movement Disorders/diagnostic imaging , Movement Disorders/therapy , Aged , Aged, 80 and over , Brain Mapping/methods , Deep Brain Stimulation/methods , Electrodes, Implanted , Female , Humans , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neuroimaging/methods
18.
Med Biol Eng Comput ; 58(4): 771-784, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32002754

ABSTRACT

Deep brain stimulation (DBS) is an established therapy for movement disorders such as essential tremor (ET). Positioning of the DBS lead in the patient's brain is crucial for effective treatment. Extensive evaluations of improvement and adverse effects of stimulation at different positions for various current amplitudes are performed intraoperatively. However, to choose the optimal position of the lead, the information has to be "mentally" visualized and analyzed. This paper introduces a new technique called "stimulation maps," which summarizes and visualizes the high amount of relevant data with the aim to assist in identifying the optimal DBS lead position. It combines three methods: outlines of the relevant anatomical structures, quantitative symptom evaluation, and patient-specific electric field simulations. Through this combination, each voxel in the stimulation region is assigned one value of symptom improvement, resulting in the division of stimulation region into areas with different improvement levels. This technique was applied retrospectively to five ET patients in the University Hospital in Clermont-Ferrand, France. Apart from identifying the optimal implant position, the resultant nine maps show that the highest improvement region is frequently in the posterior subthalamic area. The results demonstrate the utility of the stimulation maps in identifying the optimal implant position. Graphical abstract.


Subject(s)
Deep Brain Stimulation/methods , Surgery, Computer-Assisted/methods , Tremor/surgery , Accelerometry , Brain/diagnostic imaging , Brain/surgery , Data Visualization , Deep Brain Stimulation/adverse effects , Humans , Image Processing, Computer-Assisted , Microelectrodes , Monitoring, Intraoperative , Precision Medicine , Tremor/diagnostic imaging
19.
Mol Cancer Res ; 18(4): 612-622, 2020 04.
Article in English | MEDLINE | ID: mdl-31941754

ABSTRACT

Deregulated RNA-binding proteins (RBP), such as Argonaute 2 (AGO2), mediate tumor-promoting transcriptomic changes during carcinogenesis, including hepatocellular carcinoma (HCC). While AGO2 is well characterized as a member of the RNA-induced silencing complex (RISC), which represses gene expression through miRNAs, its role as a bona fide RBP remains unclear. In this study, we investigated AGO2's role as an RBP that regulates the MYC transcript to promote HCC. Using mRNA and miRNA arrays from patients with HCC, we demonstrate that HCCs with elevated AGO2 levels are more likely to have the mRNA transcriptome deregulated and are associated with poor survival. Moreover, AGO2 overexpression stabilizes the MYC transcript independent of miRNAs. These observations provide a novel mechanism of gene regulation by AGO2 and provide further insights into the potential functions of AGO2 as an RBP in addition to RISC. IMPLICATIONS: Authors demonstrate that the RBP Argonaute 2 stabilizes the MYC transcript to promote HCC.


Subject(s)
Argonaute Proteins/genetics , Carcinoma, Hepatocellular/genetics , Genes, myc , Liver Neoplasms/genetics , Proto-Oncogene Proteins c-myc/genetics , Animals , Argonaute Proteins/metabolism , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Heterografts , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mice , Mice, Inbred NOD , Mice, Nude , Mice, SCID , Proto-Oncogene Proteins c-myc/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transfection
20.
ACG Case Rep J ; 6(6): e00117, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31616777

ABSTRACT

A transplant hepatic artery pseudoaneurysm is a rare postorthotopic liver transplant complication. Bleeding is a common complication of posterior duodenal ulcer secondary to erosion into the gastroduodenal artery. We report the case of a post-transplant patient who presented with massive upper gastrointestinal hemorrhage in the setting of nonsteroidal anti-inflammatory drug use. Endoscopy demonstrated a duodenal ulcer with high-risk stigmata not amenable to hemostasis. Subsequently, an arteriogram revealed a hepatic artery pseudoaneurysm. Transplant professionals should be aware of the possibility of an ulcer eroding into the liver vasculature and in the differential diagnosis for bleeding and pseudoaneurysms in post-transplant patients.

SELECTION OF CITATIONS
SEARCH DETAIL
...