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1.
Exp Clin Transplant ; 22(4): 311-313, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38742323

RESUMEN

Biliary strictures afterlivertransplant are amenable to endoscopic dilatation or percutaneous dilatation and stenting in most cases. In rare cases, for recurrence or tight stricture, surgery is required, and hepaticojejunostomy is the favored procedure. We report a case of posttransplant stricture in a duct-to-duct anastomosis that could not be accessed due to prior gastric bypass. Despite multiple percutaneous transhepatic cholangiography dilatations, the stricture recurred, and the patient was taken up for bilioenteric bypass. During surgery, dense adhesions in the infracolic compartment with chronically twisted jejunal loops, due to prior mini gastric bypass, were encountered, which prevented the creation of a jejunal Roux limb. Hepaticoduodenostomy was performed with no recurrence of stricture at 12 months. Hepaticoduodenostomy is a viable option for surgical management of recurrent biliary strictures, especially in a setting of prior bariatric/diversion procedures.


Asunto(s)
Duodenostomía , Trasplante de Hígado , Recurrencia , Reoperación , Humanos , Trasplante de Hígado/efectos adversos , Constricción Patológica , Resultado del Tratamiento , Colestasis/etiología , Colestasis/cirugía , Colestasis/diagnóstico por imagen , Persona de Mediana Edad , Anastomosis Quirúrgica , Femenino , Masculino , Colangiografía
2.
Artículo en Inglés | MEDLINE | ID: mdl-38630420

RESUMEN

BACKGROUND: Living donor liver transplant (LDLT) is based on the principle of double equipoise. Organ shortage in Asian countries has led to development of high-volume LDLT programs with good outcomes. Safety of live liver donor is the Achilles heel of LDLT program and every effort should be made to achieve low morbidity and near zero mortality rates. METHODS: We retrospectively analyzed our prospectively maintained donor morbidity data (outcomes) of 177 donors in a new transplant program setup in western India by an experienced surgeon. The primary end point was to analyze the morbidity rates and the factors associated with it. RESULTS: None of the donors in our cohort of 177 donors developed grade IV or V complication (Clavien-Dindo classification). One-fourth (1/4th) of the donors developed complications ranging from grade I to grade III(b). The rate of complications according to modified Clavien-Dindo classification is as follows: (1) grade I in 5.6% (n = 10), (2) grade II in 14.6% (n = 26), (3) grade III(a) in 3.9% (n = 7), (4) grade III(b) in 2.2% (n = 4). Three donors (1.6%) developed post-hepatectomy intra-abdominal bleeding and required re-exploration (grade IIIb). All of them recovered well post-surgery and are doing well in follow-up. The mean follow-up of the entire cohort was 2871 ± 521 days (range 1926-3736 days). CONCLUSION: Donor safety (outcome) is determined by meticulous donor surgery and good-quality remnant.

3.
Exp Clin Transplant ; 21(11): 879-882, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-38140931

RESUMEN

OBJECTIVES: The recipient's gastroduodenal artery is often ligated before the hepatic artery anastomosis during orthotopic liver transplant, to gain either mobility or length of recipient's hepatic artery, potentially protecting the anastomosis by preventing "steal syndrome." In this study, our aim was to evaluate the consequences of gastroduodenal artery ligation and its effect on prevention of hepatic artery thrombosis. MATERIALS AND METHODS: We retrospectively analyzed deceased-donor orthotopic liver transplant procedures (n = 210) performed at a single center between January 2016 and July 2021 to compare outcomes between recipients with (group 1) and recipients without (group 2) gastroduodenal artery ligation. Group 1 included 78 patients (37%), in which the recipient's common hepatic artery was used for arterial anastomosis; group 2 included 132 patients (63%), in which the right hepatic artery orthe proper hepatic artery was used for arterial anastomosis. Occurrences of hepatic artery thrombosis, postoperative hyperamylasemia, nausea and vomiting, and delayed feeding were compared between the groups. RESULTS: There was no incidence of hepatic artery thrombosis reported in either group. In group 1, 31 patients (39.7%) were reported to have postoperative hyperamylasemia, ranging from 200 to 4700 U/L accompanied by delayed feeding, whereas, in group 2, only 16 of 132 patients (12%) had postoperative hyperamylasemia, ranging from 200 to 1400 U/L (P < .01). CONCLUSIONS: Ligation of recipient's gastroduodenal artery is not associated with decreased risk of hepatic artery thrombosis compared with nonligation. However, the procedure does have consequences in the form of possible postoperative hyperamylasemia, leading to delayed feeding probably due to decreased oral tolerance.


Asunto(s)
Hiperamilasemia , Hepatopatías , Trasplante de Hígado , Trombosis , Humanos , Arteria Hepática/cirugía , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Estudios Retrospectivos , Hiperamilasemia/complicaciones , Hepatopatías/complicaciones , Trombosis/etiología , Trombosis/prevención & control , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos
4.
Ann Transplant ; 26: e926979, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33510125

RESUMEN

BACKGROUND Reconstruction of the hepatic arterial inflow can be technically demanding in living donor liver transplantation, and thrombosis can result in graft loss and mortality. We describe the safe and reproducible "W" technique to reconstruct the hepatic artery and outcomes before and after adoption of the technique in a consecutive series of liver transplants at 2 high-volume living donor liver transplant centers. MATERIAL AND METHODS Prospectively collected data were analyzed to compare the outcomes before and after introduction of a standardized "W" technique for reconstruction of the hepatic artery in 2 high-volume living donor liver transplant programs. RESULTS In a consecutive series of 675 liver transplants, of which 27 were deceased donor transplants and 648 were living donor transplants, 443 transplants were performed with a standard interrupted reconstruction of the hepatic artery under loupes. These transplants were performed by a single surgeon, with an incidence of hepatic artery thrombosis of 2%. After introduction of the "W" technique, despite the arterial reconstruction being done by several surgeons in the early part of their learning curve, the incidence of hepatic artery thrombosis decreased to 0.86% in the next 232 transplants. CONCLUSIONS The "W" technique is a simple, easy to learn and teach technique for reconstruction of the hepatic artery without the use of the operating microscope in living donor liver transplantation.


Asunto(s)
Arteria Hepática , Trasplante de Hígado , Donadores Vivos , Procedimientos de Cirugía Plástica , Procedimientos Quirúrgicos Vasculares/métodos , Arteria Hepática/cirugía , Humanos , Procedimientos de Cirugía Plástica/métodos
5.
Am J Pathol ; 191(1): 79-89, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33127336

RESUMEN

The innate immune system plays a critical role in allograft rejection. Alloresponses involve numerous cytokines, chemokines, and receptors that cause tissue injury during rejection. To dissect these inflammatory mechanisms, we developed cell transplantation models in dipeptidylpeptidase-deficient F344 rats using mycophenolate mofetil and tacrolimus for partial lymphocyte-directed immunosuppression. Syngeneic hepatocytes engrafted in liver, whereas allogeneic hepatocytes were rejected but engrafted after immunosuppression. These transplants induced mRNAs for >40 to 50 cytokines, chemokines, and receptors. In allografts, innate cell type-related regulatory networks extended to granulocytes, monocytes, and macrophages. Activation of Tnfa and its receptors or major chemokine receptor-ligand subsets persisted in the long term. An examination of the contribution of Tnfa in allograft response revealed that it was prospectively antagonized by etanercept or thalidomide, which resolved cytokine, chemokine, and receptor cascades. In bioinformatics analysis of upstream regulator networks, the Cxcl8 pathway exhibited dominance despite immunosuppression. Significantly, Tnfa antagonism silenced the Cxcl8 pathway and decreased neutrophil and Kupffer cell recruitment, resulting in multifold greater engraftment of allogeneic hepatocytes and substantially increased liver repopulation in retrorsine/partial hepatectomy model. We conclude that Tnfa is a major driver for persistent innate immune responses after allogeneic cells. Neutralizing Tnfa should help in avoiding rejection and associated tissue injury in the allograft setting.


Asunto(s)
Rechazo de Injerto/inmunología , Hepatocitos/trasplante , Inmunidad Innata/inmunología , Inmunología del Trasplante/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Aloinjertos , Animales , Ratas , Ratas Endogámicas F344 , Ratas Long-Evans , Trasplante Homólogo
6.
Indian J Gastroenterol ; 37(4): 359-364, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30187299

RESUMEN

Abernethy malformation is a rare congenital anomaly in which there is direct communication between the portal and systemic venous circulation. The clinical presentation ranges from asymptomatic with incidental detection on imaging to secondary complications of disease or related to associate anomalies. This is a retrospective analysis of data from nine patients with Abernethy malformation at a single center. This is a referral center for Pediatric Cardiology and for Hepatobiliary and Pancreatic Surgery. The patients presented to the Pulmonary Hypertension Clinic/the Hepatobiliary Surgery Clinic. Out of nine patients, four were male. Type II Abernethy malformation was present in five patients whereas three patients had type I malformation. One of the patients had communication between inferior mesenteric vein and internal iliac vein. Five out of nine patients were erroneously diagnosed as idiopathic primary pulmonary hypertension and were treated with vasodilators. One patient required living donor liver transplant. One patient was managed with surgical shunt closure whereas two patients required transcatheter shunt closure. The rest of the patients were managed conservatively. Abernethy malformation is more common than previously thought and the diagnosis is often missed. There are various management options for Abernethy malformation, which includes surgical or transcatheter shunt closure and liver transplant. Management of Abernethy malformation depends upon type, presentation, and size of shunt.


Asunto(s)
Vena Ilíaca/anomalías , Venas Mesentéricas/anomalías , Vena Porta/anomalías , Vena Cava Inferior/anomalías , Adolescente , Adulto , Niño , Preescolar , Diagnóstico Diferencial , Errores Diagnósticos , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , India , Trasplante de Hígado , Masculino , Derivación Portosistémica Quirúrgica/métodos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
7.
Ann Hepatol ; 17(3): 426-436, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29735782

RESUMEN

INTRODUCTION AND AIM: 1. Study of liver explants - Etiologic types of end-stage chronic liver disease (ESCLD) and acute liver failure (ALF) in adults and children. 2. Assessment of donor steatosis and incidental granulomas. 3. Post-transplant liver biopsies. MATERIAL AND METHODS: Specimens of 180 explant hepatectomies, 173 donor wedge and 30 core liver biopsies, and 58 post transplant liver biopsies received in our department from April 2013 to March 2017. RESULTS: 1. Most common causes of ESCLD in adults were: alcohol related (30.32%), hepatitis virus related (18.71%) and non-alcoholic steatohepatitis related (18.06%); and in children ≤ 12 years were: biliary atresia (27.27%), autoimmune disease (18.18%) and Wilson's disease (18.18%). Most common causes of ALF in adults and children were anti-tubercular therapy induced and idiopathic respectively. 2. Prevalence rate of moderate steatosis (between 30-60%) was 4.28%. Incidental granulomas were seen in 5 cases. 3. Most common diagnoses of post-transplant biopsies in adults included acute cellular rejection (ACR) (36.17%), recurrence of viral disease (8.51%) and moderate non-specific portal triaditis (8.51%). Among children ≤ 12 years, most common diagnoses included unremarkable liver parenchyma, ACR and ischemia/reperfusion injury. CONCLUSION: 1. Alcohol- and hepatitis- virus related ESCLD, and biliary atresia are leading indications for liver transplantation in adults and children respectively. 2. Prevalence of 4.28% of moderate steatosis, is much lower than that documented in western literature. Only 5 cases of incidental granulomas is unexpectedly low in a country endemic for tuberculosis. 3. Most common diagnoses of post-transplant liver biopsies in adults has been acute rejection, which is similar to the findings from much larger published series.


Asunto(s)
Enfermedad Hepática en Estado Terminal/cirugía , Fallo Hepático Agudo/cirugía , Trasplante de Hígado , Centros de Atención Terciaria , Adolescente , Adulto , Factores de Edad , Anciano , Atresia Biliar/epidemiología , Atresia Biliar/cirugía , Biopsia , Niño , Preescolar , Selección de Donante , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/epidemiología , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/epidemiología , Hepatitis Viral Humana/epidemiología , Hepatitis Viral Humana/cirugía , Humanos , India/epidemiología , Lactante , Hepatopatías Alcohólicas/epidemiología , Hepatopatías Alcohólicas/cirugía , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/epidemiología , Trasplante de Hígado/efectos adversos , Donadores Vivos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/cirugía , Prevalencia , Recurrencia , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
8.
Indian J Gastroenterol ; 37(2): 133-140, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29594724

RESUMEN

BACKGROUND/AIM: Right lobe living donor (2/3rd partial hepatectomy) model is the best way to accurately study liver regeneration process in human beings. We aimed to study the kinetics of liver regeneration after 2/3rd partial hepatectomy in donors. METHODS: Retrospective analysis of prospectively maintained volumetric recovery data in donors was performed in 23 donors, who underwent 29 contrast-enhanced computed tomography within 3 months for various clinical indications. RESULTS: The absolute volumetric growth percentages were as follows: 37.60 ± 21.74 at 1st week, 92 ± 53.27 at 2nd week, 115.55 ± 59.65 at 4th week, and 110.79 ± 64.47 at 3 months. On sub-group analysis of our cohort, we found that 4.3%, 17%, 30.4%, and 39% donors attended ≥ 90% volumetric recovery at 1st, 2nd, 4th week, and 3 months, respectively. One patient at 4th week revealed 128% volumetric recovery. There was one more patient who exceeded original total liver volumes (TLV) (111% of TLV) at 2.5 months. The serum bilirubin and INR values peaked at postoperative day (POD) 3rd and then started showing a downward trend from POD 5th onwards. CONCLUSION: Our study is the first to document complete volumetric recovery in donors as early as 3 weeks. Two of the donors overshot their original TLV during the early regenerative phase.


Asunto(s)
Hepatectomía/métodos , Regeneración Hepática/fisiología , Trasplante de Hígado , Hígado/fisiología , Donadores Vivos , Donantes de Tejidos , Adulto , Bilirrubina/sangre , Biomarcadores/sangre , Femenino , Humanos , Relación Normalizada Internacional , Hígado/patología , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Estudios Retrospectivos , Factores de Tiempo , Adulto Joven
10.
Indian J Gastroenterol ; 36(3): 243-247, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28560633

RESUMEN

Nonalcoholic steatohepatitis (NASH) with morbid obesity and metabolic syndrome is now a common cause of end-stage liver disease (ESLD). These patients are high-risk candidates for liver transplant, and require bariatric surgery to prevent recurrent disease in the new liver. Data reports bariatric surgery after transplant, which maybe difficult because of adhesions between the stomach and liver in living donor liver transplant (LDLT) recipient. We report the first case of combined LDLT with sleeve gastrectomy (SG) from India. A morbidly obese diabetic woman with NASH-related ESLD was planned for combined right lobe LDLT with open SG, in view of failed diet therapy, musculo-skeletal complaints, and restricted mobility. Postoperatively, with liver graft functioning adequately, bariatric diet restrictions resulted in maximum reduction of 25% weight, achieving a target BMI below 30 kg/m2 within 2 months, along with complete cure of diabetes and better ambulation. Thus, combination of LDLT and bariatric surgery in the same sitting is safe and effective in management of metabolic syndrome and associated NASH-related ESLD.


Asunto(s)
Cirugía Bariátrica/métodos , Enfermedad Hepática en Estado Terminal/etiología , Enfermedad Hepática en Estado Terminal/cirugía , Gastrectomía/métodos , Trasplante de Hígado/métodos , Hígado/cirugía , Donadores Vivos , Síndrome Metabólico/complicaciones , Síndrome Metabólico/cirugía , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/cirugía , Obesidad/complicaciones , Obesidad/cirugía , Complicaciones de la Diabetes , Femenino , Humanos , India , Persona de Mediana Edad , Resultado del Tratamiento
11.
J Hepatol ; 65(6): 1171-1178, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27422749

RESUMEN

BACKGROUND & AIMS: For liver-directed cell therapy, efficient engraftment of transplanted cells is critical. This study delineated whether anti-inflammatory and endothelial disrupting properties of thalidomide could promote transplanted cell engraftment and proliferation in liver. METHODS: We used dipeptidyl peptidase IV-deficient rats for cell transplantation studies, including gene expression analysis, morphological tissue analysis, serological assays, cell culture assays, and assays of transplanted cell engraftment and proliferation. RESULTS: Thalidomide-pretreatment increased engraftment and proliferation of transplanted hepatocytes due to decreased inflammation. Moreover, thalidomide exacerbated cell transplantation-induced endothelial injury. This combined anti-inflammatory and endothelial injury effect of thalidomide was superior to the anti-inflammatory effect alone of repertaxin or etanercept, which block cytokines/chemokines/receptor-dependent inflammation. In thalidomide-pretreated animals, liver repopulation accelerated, including when cells were primed with bosentan to block endothelin-1 receptors. CONCLUSIONS: Thalidomide improved transplanted cell engraftment and liver repopulation. Therefore, this class of drugs will advance applications of liver cell therapy in people. LAY SUMMARY: This work aimed to develop effective drug treatments for improving engraftment of transplanted cells because that constitutes a critical step in rebuilding liver with healthy cells. Studies in animal models of cell transplantation led to identification of an old drug, thalidomide, which blocked inflammation and altered the liver microenvironment to yield superior engraftment and proliferation of transplanted cells. This will be appropriate for liver cell therapy in people.


Asunto(s)
Inflamación , Animales , Hepatocitos , Hígado , Ratas , Ratas Endogámicas F344 , Talidomida
13.
Indian J Surg ; 77(3): 195-9, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26246701

RESUMEN

A proportion of the operations performed in a surgical gastroenterology department are unplanned repeat laparotomies for complications of the original procedure. We examined why, in our department, these 'redo' laparotomies were performed and what was their outcome. We retrospectively analyzed 6530 patients operated between September 1996 - December 2010, of these 257 redo laparotomies were performed in 193(2.5 %) patients. There were 138 males and 55 females who had a mean age of 42 years (range 7-68 years). Eighty one (42 %) of the index surgeries were elective and 112 (58 %) performed in the emergency situation. Pancreas was the commonest organ for the index operation {50 (25.9 %)}, followed by the colon and rectum {45 (23.3 %)} and the small bowel {36 (18.7 %)}. Postoperative bleeding was the most common cause for re-exploration 66 (34.2 %) followed by an abscess or fluid collection that required surgical drainage 57 (29.6 %). The mortality rate after redo laparotomies was 33.2 % with sepsis and multi-organ failure being the commonest cause of death. Urgent redo-laparotomies that are performed following complicated abdominal operations have a high mortality rate. Postoperative bleeding, intrabdominal abscess and peritonitis are the commonest cause for redo-laparotomy. Multiple redolaparotomies and associated co-morbid conditions are significant predictors of mortality.

14.
J Gastrointest Surg ; 19(5): 935-42, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25691114

RESUMEN

The implementation of a surgical safety checklist is said to minimize postoperative surgical complications. However, to our knowledge, no randomized controlled study has been done on the influence of checklists on postoperative outcomes in a developing country. We conducted a prospective randomized controlled study with parallel group study design of the implementation of WHO surgical safety checklist involving 700 consecutive patients undergoing operations in our hospital between February 2012 and April 2013. In 350 patients, the checklist was implemented with modifications-the Rc arm. The control group of 350 patients was termed the Rn arm. The checklist was filled in by a surgery resident, and only the participants in the study were blinded. Postoperative wound-related (p = 0.04), abdominal (p = 0.01), and bleeding (p = 0.03) complications were significantly lower in the Rc compared to the Rn group. The number of overall and higher-grade complications (Clavien-Dindo grades 3 and 4) per patient reduced from 0.97 and 0.33 in the Rn arm to 0.80 and 0.23 in the Rc arm, respectively. A significant reduction in mortality was noted in the Rc arm as compared to the Rn arm (p = 0.04). In a subgroup analysis, the number of overall and higher-grade complications per patient with incomplete checklists was higher than that with fully completed checklist group. Implementation of WHO surgical safety checklist results in a reduction in mortality as well as improved postoperative outcomes in a tertiary care hospital in a developing country.


Asunto(s)
Lista de Verificación , Seguridad del Paciente , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios , Países en Desarrollo , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos
15.
Indian J Surg ; 77(Suppl 3): 843-9, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27011468

RESUMEN

In Western countries, acute mesenteric ischaemia is commonly due to arterial occlusion and occurs in patients who are usually in their seventh decade. A venous cause for intestinal gangrene has been reported in only about 10 %. We examined whether this was so in India and compared the clinical features of patients with mesenteric arterial and venous ischaemia and relate these to their ultimate prognosis. We studied retrospectively, the records of all patients admitted or referred to the department with a diagnosis of acute mesenteric ischaemia between January 1997 and October 2012, noting their demographic details and mode of presentation, the results of preoperative imaging and blood investigations, the extent of bowel ischaemia, and the length of bowel that was resected at operation and their outcome. There were 117 patients, 85 males and 32 females whose median age was 53 years. Mesenteric venous thrombosis was seen in 56 patients (48 %) and mesenteric arterial occlusion in 61 (52 %). Forty six patients died (39 %); 15 with venous occlusion (27 %) and 31 with arterial occlusion (51 %). Compared to patients with arterial occlusion, the patients with venous obstruction were younger, had a longer duration of symptoms, were less frequently hypotensive at presentation, had higher platelet counts, had a shorter length of bowel resected, had fewer colonic resections and had a lower mortality. Other predictors of mortality on multivariate analysis were a longer duration of symptoms, lower serum albumin and higher creatinine levels at presentation and a shorter length of residual bowel. In India, acute mesenteric ischaemia in tertiary care centres is due to venous thrombosis in almost half of the patients who are at least a decade younger than those in the West. Significant predictors of mortality include low serum albumin and raised creatinine levels, a shorter residual bowel length and an arterial cause for mesenteric ischaemia.

17.
Am J Nucl Med Mol Imaging ; 4(6): 537-47, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25250203

RESUMEN

Identification by molecular imaging of key processes in handling of transition state metals, such as copper (Cu), will be of considerable clinical value. For instance, the ability to diagnose Wilson's disease with molecular imaging by identifying copper excretion in an ATP7B-dependent manner will be very significant. To develop highly effective diagnostic approaches, we hypothesized that targeting of radiocopper via the asialoglycoprotein receptor will be appropriate for positron emission tomography, and examined this approach in a rat model of Wilson's disease. After complexing (64)Cu to asialofetuin we studied handling of this complex compared with (64)Cu in healthy LEA rats and diseased homozygous LEC rats lacking ATP7B and exhibiting hepatic copper toxicosis. We analyzed radiotracer clearance from blood, organ uptake, and biliary excretion, including sixty minute dynamic positron emission tomography recordings. In LEA rats, (64)Cu-asialofetuin was better cleared from blood followed by liver uptake and greater biliary excretion than (64)Cu. In LEC rats, (64)Cu-asialofetuin activity cleared even more rapidly from blood followed by greater uptake in liver, but neither (64)Cu-asialofetuin nor (64)Cu appeared in bile. Image analysis demonstrated rapid visualization of liver after (64)Cu-asialofetuin administration followed by decreased liver activity in LEA rats while liver activity progressively increased in LEC rats. Image analysis resolved this difference in hepatic activity within one hour. We concluded that (64)Cu-asialofetuin complex was successfully targeted to the liver and radiocopper was then excreted into bile in an ATP7B-dependent manner. Therefore, hepatic targeting of radiocopper will be appropriate for improving molecular diagnosis and for developing drug/cell/gene therapies in Wilson's disease.

18.
Am J Pathol ; 184(10): 2779-90, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25128377

RESUMEN

Despite the potential of ischemic preconditioning for organ protection, long-term effects in terms of molecular processes and cell fates are ill defined. We determined consequences of hepatic ischemic preconditioning in rats, including cell transplantation assays. Ischemic preconditioning induced persistent alterations; for example, after 5 days liver histology was normal, but γ-glutamyl transpeptidase expression was observed, with altered antioxidant enzyme content, lipid peroxidation, and oxidative DNA adducts. Nonetheless, ischemic preconditioning partially protected from toxic liver injury. Similarly, primary hepatocytes from donor livers preconditioned with ischemia exhibited undesirably altered antioxidant enzyme content and lipid peroxidation, but better withstood insults. However, donor hepatocytes from livers preconditioned with ischemia did not engraft better than hepatocytes from control livers. Moreover, proliferation of hepatocytes from donor livers preconditioned with ischemia decreased under liver repopulation conditions. Hepatocytes from donor livers preconditioned with ischemia showed oxidative DNA damage with expression of genes involved in MAPK signaling that impose G1/S and G2/M checkpoint restrictions, including p38 MAPK-regulated or ERK-1/2-regulated cell-cycle genes such as FOS, MAPK8, MYC, various cyclins, CDKN2A, CDKN2B, TP53, and RB1. Thus, although ischemic preconditioning allowed hepatocytes to better withstand secondary insults, accompanying DNA damage and molecular events simultaneously impaired their proliferation capacity over the long term. Mitigation of ischemic preconditioning-induced DNA damage and deleterious molecular perturbations holds promise for advancing clinical applications.


Asunto(s)
Isquemia/patología , Precondicionamiento Isquémico , Hígado/irrigación sanguínea , Daño por Reperfusión/prevención & control , Transducción de Señal , Animales , Tetracloruro de Carbono/toxicidad , Proliferación Celular , Daño del ADN , Dipeptidil Peptidasa 4/deficiencia , Dipeptidil Peptidasa 4/genética , Modelos Animales de Enfermedad , Hepatocitos/metabolismo , Humanos , Peroxidación de Lípido , Hígado/lesiones , Hígado/metabolismo , Estrés Oxidativo , Ratas , gamma-Glutamiltransferasa/genética , gamma-Glutamiltransferasa/metabolismo
19.
Hepatology ; 60(4): 1378-88, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24844924

RESUMEN

UNLABELLED: Engraftment of transplanted cells is critical for liver-directed cell therapy, but most transplanted cells are rapidly cleared from liver sinusoids by proinflammatory cytokines/chemokines/receptors after activation of neutrophils or Kupffer cells (KCs). To define whether tumor necrosis factor alpha (TNF-α) served roles in cell-transplantation-induced hepatic inflammation, we used the TNF-α antagonist, etanercept (ETN), for studies in syngeneic rat hepatocyte transplantation systems. After cell transplantation, multiple cytokines/chemokines/receptors were overexpressed, whereas ETN before cell transplantation essentially normalized these responses. Moreover, ETN down-regulated cell-transplantation-induced intrahepatic release of secretory cytokines, such as high-mobility group box 1. These effects of ETN decreased cell-transplantation-induced activation of neutrophils, but not of KCs. Transplanted cell engraftment improved by several-fold in ETN-treated animals. These gains in cell engraftment were repeatedly realized after pretreatment of animals with ETN before multiple cell transplantation sessions. Transplanted cell numbers did not change over time, indicating absence of cell proliferation after ETN alone. By contrast, in animals preconditioned with retrorsine and partial hepatectomy, cell transplantation after ETN pretreatment significantly accelerated liver repopulation, compared to control rats. CONCLUSION: TNF-α plays a major role in orchestrating cell-transplantation-induced inflammation through regulation of multiple cytokines/chemokines/receptor expression. Because TNF-α antagonism by ETN decreased transplanted cell clearance, improved cell engraftment, and accelerated liver repopulation, this pharmacological approach to control hepatic inflammation will help optimize clinical strategies for liver cell therapy.


Asunto(s)
Proliferación Celular/fisiología , Trasplante de Células , Hepatocitos/trasplante , Inmunoglobulina G/uso terapéutico , Inflamación/prevención & control , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Citocinas/metabolismo , Etanercept , Inmunoglobulina G/farmacología , Inflamación/fisiopatología , Macrófagos del Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hígado/cirugía , Modelos Animales , Neutrófilos/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/fisiología
20.
Indian J Gastroenterol ; 33(4): 369-74, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24756424

RESUMEN

BACKGROUND: Complications following liver transplantation requiring readmission may be serious and potentially life threatening. Most reports on readmission have been about after deceased donor liver transplantation (DDLT). We hypothesized that readmission after living donor liver transplantation (LDLT) is due to different reasons and analyzed our experience. METHODS: We retrospectively analyzed the records of 172 consecutive patients who underwent liver transplantation at our institute between January 2010 and June 2012. The primary outcome measure was readmission. We classified readmission into early (<3 months after discharge) and late (>3 months). RESULTS: The study population was 140 after excluding pediatric patients (12), DDLT recipients (2), and those who died during the index admission (18). Their median age was 42 years, and there were 117 males and 23 females. Thirty-eight patients were readmitted (56 episodes) after LDLT. There were 35 early and 21 late readmission episodes. The most common cause for early readmissions was infection (46 %) and that for late readmissions was biliary stricture (62 %). On univariate analysis, pretransplant portal vein thrombosis, more than one bile duct in the liver graft, revised arterial anastomosis or two arteries in the graft, and higher serum alkaline phosphatase levels at discharge were significantly associated with readmission. Readmission was also significantly associated with a higher overall mortality than non-readmission in which there was no mortality. CONCLUSION: Pretransplant portal vein thrombosis, more than one bile duct in the liver graft, revision of the arterial anastomosis or two arteries in the graft, and higher serum alkaline phosphatase levels at discharge were significantly associated with readmission. Infective and biliary complications were the commonest causes of early and late readmission after LDLT.


Asunto(s)
Trasplante de Hígado/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Adulto , Fosfatasa Alcalina/sangre , Anastomosis Quirúrgica , Conductos Biliares , Colestasis/epidemiología , Femenino , Humanos , Infecciones/epidemiología , Hígado/anatomía & histología , Hígado/irrigación sanguínea , Donadores Vivos , Masculino , Vena Porta , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Trombosis de la Vena
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