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1.
Front Surg ; 9: 861575, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35310425
2.
Ann Surg Open ; 3(4): e221, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37600287

RESUMEN

To compare the outcomes of modified-Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) techniques with those of conventional-ALPPS. Background: ALPPS is an established technique for treating advanced liver tumors. Methods: PubMed, Web of Science, and Cochrane databases were searched. The outcomes were assessed by single-arm and 2-arm analyses. Results: Seventeen studies containing 335 modified-ALPPS patients were included in single-arm meta-analysis. The estimated blood loss was 267 ± 29 mL (95% confidence interval [CI], 210-324 mL) during the first and 662 ± 51 mL (95% CI, 562-762 mL) during the second stage. The operation time was 166 ± 18 minutes (95% CI, 131-202 minutes) during the first and 225 ± 19 minutes (95% CI, 188-263 minutes) during the second stage. The major morbidity rate was 14% (95% CI, 9%-22%) after the first stage. The future liver remnant hypertrophy rate was 65.2% ± 5% (95% CI, 55%-75%) and the interstage interval was 16 ± 1 days (95% CI, 14-17 days). The dropout rate was 9% (95% CI, 5%-15%). The overall complication rate was 46% (95% CI, 37%-56%) and the major complication rate was 20% (95% CI, 14%-26%). The postoperative mortality rate was 7% (95% CI, 4%-11%). Seven studies containing 215 patients were included in comparative analysis. The hypertrophy rate was not different between 2 methods (mean difference [MD], -5.01; 95% CI, -19.16 to 9.14; P = 0.49). The interstage interval was shorter for partial-ALPPS (MD, 9.43; 95% CI, 3.29-15.58; P = 0.003). The overall complication rate (odds ratio [OR], 10.10; 95% CI, 2.11-48.35; P = 0.004) and mortality rate (OR, 3.74; 95% CI, 1.36-10.26; P = 0.01) were higher in the conventional-ALPPS. Conclusions: The hypertrophy rate in partial-ALPPS was similar to conventional-ALPPS. This shows that minimizing the first stage of the operation does not affect hypertrophy. Moreover, the postoperative overall morbidity and mortality rates were lower following partial-ALPPS.

3.
Transpl Int ; 34(5): 778-800, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33728724

RESUMEN

This study aimed to identify cutoff values for donor risk index (DRI), Eurotransplant (ET)-DRI, and balance of risk (BAR) scores that predict the risk of liver graft loss. MEDLINE and Web of Science databases were searched systematically and unrestrictedly. Graft loss odds ratios and 95% confidence intervals were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Cutoff values for predicting graft loss at 3 months, 1 year, and 3 years were analyzed for each of the scores. Measures of calibration and discrimination used in studies validating the DRI and the ET-DRI were summarized. DRI ≥ 1.4 (six studies, n = 35 580 patients) and ET-DRI ≥ 1.4 (four studies, n = 11 666 patients) were associated with the highest risk of graft loss at all time points. BAR > 18 was associated with the highest risk of 3-month and 1-year graft loss (n = 6499 patients). A DRI cutoff of 1.8 and an ET-DRI cutoff of 1.7 were estimated using a summary receiver operator characteristic curve, but the sensitivity and specificity of these cutoff values were low. A DRI and ET-DRI score ≥ 1.4 and a BAR score > 18 have a negative influence on graft survival, but these cutoff values are not well suited for predicting graft loss.


Asunto(s)
Trasplante de Hígado , Supervivencia de Injerto , Humanos , Trasplante de Hígado/efectos adversos , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos
4.
Medicine (Baltimore) ; 99(39): e22180, 2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-32991411

RESUMEN

BACKGROUND: Tacrolimus-based immunosuppression has resulted in enormous improvements on liver transplantation (LTx) outcomes. However, dose adjustment and medication adherence play a key role in post-transplant treatment success. The aim of the present study is to assess the trough levels and the need for adaptation of therapeutic doses in de novo LTx patients treated with Tacrolimus in the clinical routine, without any intervention to the treatment regimen. METHODS AND ANALYSIS: This is a pilot, prospective, exploratory, monocentric, non-interventional and non-randomized investigator-initiated study. Prospectively maintained data of 100 patients treated with various oral Tacrolimus-based immunosuppressants (Prograf or Envarsus) will be analyzed. The number of required dose adjustments of Tacrolimus formulations used in clinical routine for achieving the target trough level, Tacrolimus trough level, Tacrolimus dosing, concentration/dose ratio, routine laboratory tests, efficacy data (incl. survival, acute rejection, re-transplantation), patients therapy adherence, and infections requiring the need to reduce individual immunosuppressant dosing will be evaluated for each patient. RESULT: This study will evaluate the trough levels and the need for adaptation of therapeutic doses in de novo LTx patients treated with Tacrolimus in the clinical routine, without any intervention to the treatment regimen. CONCLUSION: The HDTACRO study will be the first study to systematically and prospectively evaluate various oral Tacrolimus-based immunosuppressants in de novo liver transplanted patients. If a difference between the therapy-subgroups is evident at the end of the trial, a randomized control trial will eventually be designed. Registration number: ClinicalTrials.gov: NCT04444817.


Asunto(s)
Terapia de Inmunosupresión/métodos , Inmunosupresores/administración & dosificación , Trasplante de Hígado , Tacrolimus/administración & dosificación , Administración Oral , Relación Dosis-Respuesta a Droga , Humanos , Cumplimiento de la Medicación , Proyectos Piloto , Estudios Prospectivos
5.
Front Immunol ; 11: 1222, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32625210

RESUMEN

Background: The systemic inflammatory cascade triggered in donors after brain death enhances the ischemia-reperfusion injury after organ transplantation. Intravenous steroids are routinely used in the intensive care units for the donor preconditioning. Immunosuppressive medications could be potentially used for this purpose as well. Data regarding donor preconditioning with calcineurin inhibitors or inhibitors of mammalian target for Rapamycin is limited. The aim of this project is to investigate the effects of (oral) donor preconditioning with a calcineurin inhibitor (Cyclosporine) vs. an inhibitor of mammalian target for Rapamycin (Everolimus) compared to the conventional administration of steroid in the setting of donation after brain death in porcine renal transplantation. Methods: Six hours after the induction of brain death, German landrace donor pigs (33.2 ± 3.9 kg) were randomly preconditioned with either Cyclosporine (n = 9) or Everolimus (n = 9) administered via nasogastric tube with a repeated dose just before organ procurement. Control donors received intravenous Methylprednisolone (n = 8). Kidneys were procured, cold-stored in Histidine-Tryptophane-Ketoglutarate solution at 4°C and transplanted in nephrectomized recipients after a mean cold ischemia time of 18 h. No post-transplant immunosuppression was given to avoid confounding bias. Blood samples were obtained at 4 h post reperfusion and daily until postoperative day 5 for complete blood count, blood urea nitrogen, creatinine, and electrolytes. Graft protocol biopsies were performed 4 h after reperfusion to assess early histological and immunohistochemical changes. Results: There was no difference in the hemodynamic parameters, hemoglobin/hematocrit and electrolytes between the groups. Serum blood urea nitrogen and creatinine peaked on postoperative day 1 in all groups and went back to the preoperative levels at the conclusion of the study on postoperative day 5. Histological assessment of the kidney grafts revealed no significant differences between the groups. TNF-α expression was significantly lower in the study groups compared with Methylprednisolone group (p = 0.01) Immunohistochemistry staining for cytochrome c showed no difference between the groups. Conclusion: Oral preconditioning with Cyclosporine or Everolimus is feasible in donation after brain death pig kidney transplantation and reduces the expression of TNF-α. Future studies are needed to further delineate the role of oral donor preconditioning against ischemia-reperfusion injury.


Asunto(s)
Muerte Encefálica , Inhibidores de la Calcineurina/administración & dosificación , Precondicionamiento Isquémico/métodos , Trasplante de Riñón , Inhibidores de Proteínas Quinasas/administración & dosificación , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Donantes de Tejidos , Animales , Biomarcadores , Humanos , Inmunohistoquímica , Inmunosupresores/administración & dosificación , Preservación de Órganos/métodos , Porcinos , Obtención de Tejidos y Órganos/métodos
6.
Exp Clin Transplant ; 18(3): 320-324, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32039670

RESUMEN

OBJECTIVES: Spontaneous splenorenal shuntis a type of portosystemic shunt that develops frequently in the setting of chronic portal hypertension. It remains controversial whether shuntinterventions during liver transplant improve transplant outcomes. MATERIALS AND METHODS: We conducted a retrospective comparison between deceased-donor liver transplant recipients who received spontaneous splenorenal shunt intervention and those who did not at a tertiary center between 2012 and 2017. Primary outcomes of interest included intraoperative transfusion requirement, hospital length of stay, acute kidney injury posttransplant, portal vein thrombosis, thrombocytopenia, and 1-year graft and patient survival. RESULTS: Of 268 liver transplant recipients, 50 (18.6%) had large spontaneous splenorenal shunts pretransplant, with 45 patients having available radiologic and outcome data. Nine of 45 patients (20%) received shunt intervention, including pretransplant balloonoccluded retrograde transvenous obliteration (n = 5), intraoperative ligation of the left renal vein (n = 3), and intraoperative direct shunt ligation (n = 1). Demographic data, clinical characteristics, and Model for End-Stage Liver Disease scores were not different between the intervention and the nonintervention groups. Intraoperative transfusion, length of hospitalization, portal vein thrombosis, thrombocytopenia, and 1-year graft and patient survival were also similar between the 2 groups. However, the rate of posttransplant acute kidney injury was significantly lower in patients in the intervention group (0 cases vs 12 cases; odds ratio = 0.73; 95% confidence interval, 0.59-0.90). Patients with no SRS intervention (n = 36) were followed radiologically for 1 year posttransplant, with follow-up data showing complete resolution of spontaneous splenorenal shunt in just 4 patients (15%) and no changes in the remaining patients. CONCLUSIONS: Peritransplant interventions for spontaneous splenorenal shunt may reduce posttransplant acute kidney injury. In patients without intervention, spontaneous splenorenal shunt predominantly persisted 1 year posttransplant.


Asunto(s)
Lesión Renal Aguda/prevención & control , Síndrome Hepatorrenal/cirugía , Fallo Renal Crónico/cirugía , Trasplante de Hígado/efectos adversos , Venas Renales/cirugía , Vena Esplénica/cirugía , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Adulto , Anciano , Femenino , Síndrome Hepatorrenal/diagnóstico por imagen , Síndrome Hepatorrenal/mortalidad , Síndrome Hepatorrenal/fisiopatología , Humanos , Incidencia , Fallo Renal Crónico/diagnóstico por imagen , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/fisiopatología , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Venas Renales/diagnóstico por imagen , Venas Renales/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Vena Esplénica/diagnóstico por imagen , Vena Esplénica/fisiopatología , Factores de Tiempo , Resultado del Tratamiento
7.
Transplantation ; 103(10): 2003-2011, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31022148

RESUMEN

The disparity between the number of available donor livers and patients awaiting a liver transplant has led transplant centers to accept suboptimal livers. There has been no universally accepted tool to predict the posttransplant function of these organs to safely increase the donor pool, protect these livers against ischemia-reperfusion injury, or improve their quality before implantation. Ex situ liver machine preservation has emerged as a promising novel graft protective strategy in the field of liver transplantation, with remarkable ongoing research and evolving clinical trials within Europe and the United States. This technology has been shown to be safe and feasible in the clinical liver transplantation field, has shown to reduce liver ischemia-reperfusion injury, and has shown to decrease the graft discard rate compared with conventional static cold storage. This review focuses on the current status of ex situ machine preservation in clinical liver transplantation, describing the most important technical aspects with the emphasis on the findings of the most recent clinical studies.


Asunto(s)
Trasplante de Hígado/efectos adversos , Preservación de Órganos/métodos , Perfusión/métodos , Daño por Reperfusión/prevención & control , Aloinjertos/irrigación sanguínea , Aloinjertos/provisión & distribución , Ensayos Clínicos como Asunto , Selección de Donante/normas , Humanos , Hígado/irrigación sanguínea , Trasplante de Hígado/métodos , Trasplante de Hígado/normas , Preservación de Órganos/instrumentación , Perfusión/instrumentación , Daño por Reperfusión/etiología
8.
Amino Acids ; 51(6): 903-911, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30941574

RESUMEN

Donor preconditioning with glycine prevents Kupffer cell-dependent reperfusion injury to liver grafts. Partial liver grafts need to regenerate and grow in size after transplantation; however, glycine inactivates Kupffer cells, which are important for hepatic regeneration. Thus, this study was designed to evaluate the impact of donor preconditioning with glycine after partial liver transplantation (pLTx). PLTx was performed in 28 female Sprague-Dawley rats. Glycine (1.5 ml, 300 mM; i.v.) was given to 14 live donors before organ procurement. Liver enzymes and histology were investigated 8 h after reperfusion to index liver injury and leukocyte infiltration. Hepatic microperfusion and leukocyte-endothelium interaction were assessed using the in vivo fluorescence microscopy method. Ki-67 and TNF-α were detected by immunohistochemistry for regeneration and Kupffer cell activation. Glycine significantly increased survival from 0% in controls to 40%, while both liver enzyme levels and necrosis were decreased to about 50% of controls (p < 0.05). Sinusoidal blood flow increased by 40-80%, while leukocyte-endothelium interaction decreased to 30% of control values (p < 0.05). While Kupffer cell-derived TNF-α decreased to 70% of controls, there was no difference between groups in Ki-67 expression. Data presented here clearly demonstrate that glycine protects partial liver grafts from reperfusion injury without effects on regeneration.


Asunto(s)
Glicina/farmacología , Regeneración Hepática/efectos de los fármacos , Trasplante de Hígado/efectos adversos , Sustancias Protectoras/farmacología , Daño por Reperfusión/prevención & control , Animales , Femenino , Antígeno Ki-67/análisis , Macrófagos del Hígado/metabolismo , Hígado/metabolismo , Regeneración Hepática/fisiología , Necrosis/prevención & control , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/análisis
9.
Eur Surg Res ; 59(1-2): 91-99, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30032156

RESUMEN

BACKGROUND: Experimental pneumoperitoneum induces ischemia/reperfusion injury (IRI) in the liver, most likely via Kupffer cell (KC)-dependent mechanisms. Glycine has been shown to ameliorate IRI in various animal models. Thus, this study was performed to assess the effects of glycine on the liver after pneumoperitoneum. MATERIALS AND METHODS: Sprague-Dawley rats (220-250 g in weight) underwent CO2 pneumoperitoneum (12 mm Hg) for 90 min. Some rats received i.v. glycine (1.5 mL, 300 mM) 10 min before pneumoperitoneum. Controls were given the same volume of Ringer's solution. Transaminases, hepatic microcirculation, and phagocytosis of latex beads indexing both liver injury and KC activation were examined following pneumoperitoneum. Analysis of variance (ANOVA), plus a subsequent t test or χ2 test (or Fisher's exact test) were carried out as appropriate. Results are presented as mean ± SEM. RESULTS: Glycine significantly decreased lactate dehydrogenase at 1 h and both aspartate aminotransferase and alanine aminotransferase at 2 h after pneumoperitoneum from 477 ± 43, 154 ± 17, and 60 ± 6 U/L in controls to 348 ± 25, 101 ± 11, and 34 ± 3 U/L, respectively (p < 0.05). In parallel, glycine significantly decreased both the rate of permanent adherence of leukocytes to the endothelium by up to 35% and the rate of phagocytosis by > 50% compared to the control group. CONCLUSION: Glycine decreased IRI after pneumoperitoneum, most likely via KC-dependent mechanisms.


Asunto(s)
Glicina/farmacología , Hígado/irrigación sanguínea , Neumoperitoneo Artificial/efectos adversos , Daño por Reperfusión/prevención & control , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Femenino , Macrófagos del Hígado/fisiología , Fagocitosis , Ratas , Ratas Sprague-Dawley
10.
Expert Rev Gastroenterol Hepatol ; 11(7): 623-631, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28438069

RESUMEN

INTRODUCTION: There have been remarkable efforts to characterize the key responsible pathophysiologic mechanisms, as well as to ameliorate the organ preservation and ischemia reperfusion injury with the ultimate goal of expanding the donor pool and further improvement of the outcomes of liver transplantation. Attempts to translate the experimental results from bench to bedside have yielded no valid protective concepts in the field of clinical liver transplantation yet. Nonetheless, there has been a considerable amount of ongoing clinical research to develop clinically relevant graft protective strategies. Areas covered: This review focuses on the most recent evidence based findings and ongoing clinical trials that might lead to emerging graft protective strategies in the field of clinical liver transplantation. New evidence-based findings in the donor preconditioning, organ preservation, and perioperative pharmacologic graft protection strategies in the recipient are reviewed. Expert commentary: Few strategies have been shown to exert some graft protective effects against ischemia reperfusion injury in recent clinical trials in liver transplantation. Among others, 'dynamic graft preservation' techniques have been emerging as more promising graft optimization strategies.


Asunto(s)
Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Precondicionamiento Isquémico , Trasplante de Hígado/métodos , Preservación de Órganos/métodos , Daño por Reperfusión/prevención & control , Anestésicos por Inhalación/uso terapéutico , Antiinflamatorios/uso terapéutico , Desflurano , Supervivencia de Injerto/efectos de los fármacos , Humanos , Isoflurano/análogos & derivados , Isoflurano/uso terapéutico , Trasplante de Hígado/efectos adversos , Éteres Metílicos/uso terapéutico , Metilprednisolona/uso terapéutico , Sevoflurano
11.
Ann Transplant ; 21: 675-682, 2016 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-27799654

RESUMEN

BACKGROUND The model for end-stage liver disease (MELD) is a laboratory-based scoring system for assessing the severity of liver disease. Since 16 December 2006, MELD-based organ allocation for liver transplantation (LT) has been established in Germany to prioritize the sickest patients. The present study was designed to evaluate the effect of using different laboratories on the calculated MELD score, despite the use of mandatory round-robin testing for comparable of inter-laboratory results. MATERIAL AND METHODS Blood samples were taken from 10 patients with liver disease. Bilirubin, creatinine, and INR were measured in 6 different laboratories. The patients' MELD scores were calculated and the inter-laboratory variability was compared. RESULTS The highest discrepancy between the laboratories was 5 MELD score points and the highest inter-laboratory difference for bilirubin, INR, and creatinine was 4.6, 1.2, and 0.99 mg/dl, respectively. Pairwise comparison of the laboratory values showed a significant inter-laboratory difference (p<0.05). CONCLUSIONS Results clearly demonstrate, for the first time, that liver allocation for LT in Germany is based on nationwide noncomparable laboratory readouts for the MELD score.


Asunto(s)
Enfermedad Hepática en Estado Terminal/sangre , Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado , Índice de Severidad de la Enfermedad , Adulto , Bilirrubina/sangre , Creatinina/sangre , Femenino , Alemania , Humanos , Relación Normalizada Internacional , Laboratorios , Cirrosis Hepática/sangre , Cirrosis Hepática/cirugía , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Obtención de Tejidos y Órganos , Listas de Espera
12.
J Invest Surg ; 29(1): 57-65, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26375577

RESUMEN

AIM OF THE STUDY: Insufficient data are available to determine the most suitable extent of intestinal resection required to induce short-bowel syndrome (SBS) in pigs. This study aimed to compare the three main SBS-models published. METHODS: A 75%, 90%, or 100% mid-intestinal resection was performed in groups of n = 5 pigs each. Clinical (body weight, stool consistency) and biochemical (serum eletrolytes, citrulline, albumin, prealbumin, and transferrin) parameters were determined daily, functional (D-xylose resorption) and histological (intestinal villus length) parameters were determined after 2 weeks. A t-test and ANOVA were used for statistical analysis. RESULTS: Only in the 100% group, we observed a persistent weight loss (13.6 ± 3.8%) and diarrhea, as well as a decrease in prealbumin-levels (41%) and transferrin levels (33%). Serum electrolytes remained stable in all groups during the observation period. Citrulline stabilized at different levels (100% group 13.9 ± 1.0 µmol/L; 90% group 18.8 ± 1.0 µmol/L; 75% group 26.3 ± 1.4 µmol/L; all p < .05). D-xylose resorption was lowest in the 100%, followed by 90% and 75% group (100% group 32.8 ± 4.9 mg/L; 90% group 50.0 ± 19.6 mg/L; 75% group 57.8 ± 8.8 mg/L; p = .393). Intestinal villus length decreased in all groups (100% group 11.0%; 90% group 14.0%; 75% group 19.1%). CONCLUSIONS: 75% intestinal resection is less suitable as an SBS model, as animals tend to recover remarkably. The 90% model is suitable for longer-term studies, as animals might survive longer due to partial compensation. Due to severe nutritional, biochemical, and physiological derangements, the 100% model can only be used for acute experiments and those immediately followed by small bowel transplantation.


Asunto(s)
Modelos Animales de Enfermedad , Mucosa Intestinal/patología , Intestino Delgado/cirugía , Síndrome del Intestino Corto , Sus scrofa , Animales , Citrulina/sangre , Diarrea/sangre , Diarrea/etiología , Electrólitos/sangre , Femenino , Intestino Delgado/irrigación sanguínea , Prealbúmina/análisis , Albúmina Sérica/análisis , Transferrina/análisis , Pérdida de Peso
13.
Mol Med ; 20: 230-7, 2014 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-24618883

RESUMEN

Chronic vascular inflammation is a key hallmark in the pathogenesis of abdominal aortic aneurysm (AAA). Recent investigations have suggested that the inflammasome, a cytosolic multiprotein complex that recognizes pathogen-associated molecular patterns, plays a role in atherosclerosis. However, its role in AAA inflammation has not yet been investigated. This pilot study analyzed inflammasome activation and its intramural localization in 24 biopsy samples from 11 patients with asymptomatic AAA versus 12 aortic samples from apparently healthy controls. Using a histological inflammation scale, we identified grade 2/3 inflammatory changes with lymphoid aggregates/tertiary lymphoid organs in 21 out of 24 AAA samples, whereas only 7 of the 12 control samples exhibited local grade 1 inflammatory changes. Strong expression levels of "apoptosis-associated speck-like protein with a caspase recruitment domain" (ASC), caspase-1, caspase-5 and "absent in melanoma 2" (AIM2) were detected by immunohistochemistry in both sporadic infiltrating lymphoid cells and lymphoid aggregates located in the outer media and adventitia of AAA samples. In contrast, inflammasome-positive cells were restricted to cholesterol plaque-associated areas and to single infiltrating cells in control aortas. Analysis of gene expression using real-time polymerase chain reaction (PCR) revealed significantly increased median mRNA levels of the inflammasome core components PYCARD (ASC), CASP1 (Caspase-1) and IL1B (IL-1ß) in AAA tissue compared with normal aorta. Moreover, significantly increased median amounts of AIM2 protein and mature caspase-5 (p20) were found in samples associated with high rupture risk compared with paired low rupture risk samples of the same AAA patient. We conclude from our data that AAA-associated lymphoid cells are capable of inflammasome signaling, suggesting that inflammasome activation is involved in the chronic inflammatory process driving AAA progression.


Asunto(s)
Aneurisma de la Aorta Abdominal/inmunología , Proteínas de Unión al ADN/inmunología , Inflamasomas/inmunología , Anciano , Anciano de 80 o más Años , Aorta Abdominal/inmunología , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/patología , Proteínas Adaptadoras de Señalización CARD , Caspasa 1/genética , Caspasa 1/inmunología , Caspasas/inmunología , Proteínas del Citoesqueleto/inmunología , Femenino , Humanos , Linfocitos/inmunología , Masculino , Persona de Mediana Edad
14.
J Pediatr Surg ; 48(8): 1794-805, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23932625

RESUMEN

PURPOSE: To compare LILT and STEP, the two principal procedures to lengthen the native bowel in children with a short bowel syndrome (SBS), by discussing the indications and presenting the outcome from published data. METHODS: A review of literature was performed. N=39 publications were reviewed. RESULTS: For LILT and STEP, failure to achieve intestinal autonomy by conservative therapy represents the main indication, and end-stage liver disease the main contraindication. A sufficiently dilated intestinal segment is a common anatomical precondition for both procedures. STEP can be performed on shorter intestinal segments and on intricate segments such as the duodenum, which is technically not feasible for LILT. Both procedures have a similar extent of intestinal lengthening (approximately 70%) and result in improvement of enteral nutrition and reversal of complications of parenteral nutrition. STEP seems to have a lower mortality and overall progression to transplantation. CONCLUSIONS: STEP and LILT are both accepted procedures for non-transplant surgical management of SBS in children. The outcome after STEP seems to be more favourable, but larger series are needed to further assess accurate selection of eligible patients and to estimate effectiveness of procedures. A considerably higher number of cases for evaluation might be accomplished through the widespread use of a centralised registry.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Síndrome del Intestino Corto/cirugía , Adolescente , Traslocación Bacteriana , Niño , Preescolar , Comorbilidad , Contraindicaciones , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Nutrición Enteral/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Intestino Delgado/trasplante , Intestinos/irrigación sanguínea , Intestinos/microbiología , Intestinos/cirugía , Fallo Hepático/epidemiología , Fallo Hepático/prevención & control , Masculino , Desnutrición/etiología , Desnutrición/prevención & control , Nutrición Parenteral/efectos adversos , Complicaciones Posoperatorias/epidemiología , Recuperación de la Función , Sepsis/epidemiología , Resultado del Tratamiento
15.
Clin Transplant ; 27 Suppl 25: 6-15, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23909497

RESUMEN

BACKGROUND: Transplantation surgery requires many years of training. This study evaluates and presents the results of our recent four-yr animal hands-on courses of transplantation surgery on participants' training. METHODS: Since 2008, five two-d hands-on courses of transplantation surgery were performed on swine models at our department. Sixty-one participants were asked to answer three questionnaires (pre-course, immediate post-course, subsequent post-course). The questions pertained to their past education, expectations, and evaluation of our courses, as well as our course's effectiveness in advancing their surgical abilities. The results were analyzed, compared and are presented herein. RESULTS: On average, 1.8 multiorgan procurements, 2.3 kidney, 1.5 liver, and 0.7 pancreas transplantations were performed by each participant. 41.7% of participants considered their previous practical training only satisfactory; 85% hoped for more opportunities to practice surgery; 73.3% evaluated our courses as very good; and 95.8% believed that our courses had fulfilled their expectations. 66% found the effectiveness of our course in advancing their surgical abilities very good; 30% good, and 4% satisfactory. CONCLUSION: Animal hands-on courses of transplantation surgery are one of the best options to learn and practice different operations and techniques in a near to clinical simulated model. Regular participation in such courses with a focus on practical issues can provide optimal opportunities for trainees with the advantage of direct mentoring and feedback.


Asunto(s)
Cirugía General/educación , Evaluación de Necesidades , Trasplante de Órganos , Adulto , Animales , Educación Médica Continua , Femenino , Humanos , Masculino , Evaluación de Programas y Proyectos de Salud , Porcinos
16.
Clin Transplant ; 27 Suppl 25: 56-65, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23909503

RESUMEN

The improvement of outcomes in intestinal transplantation (ITx) over the last two decades has been made possible through standardization in surgical techniques, improvements in immunosuppressive and induction protocols, and post-operative patient care. From a surgical technical point of view, all different types of small bowel containing transplants can be categorized into three main prototypes, including isolated small bowel, liver-small bowel, and multivisceral transplantations. In this review, we describe these three main prototypes and discuss the most important technical modifications of each type, as well as donor and recipient procedures, and highlight the more recent operative technical topics of discussion in the literature.


Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Enfermedades Intestinales/cirugía , Intestinos/trasplante , Obtención de Tejidos y Órganos , Humanos
17.
HPB Surg ; 2012: 783479, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22791934

RESUMEN

Background. Several approaches have been proposed to pharmacologically ameliorate hepatic ischemia/reperfusion injury (IRI). This study was designed to evaluate the effects of a preconditioning oral nutritional supplement (pONS) containing glutamine, antioxidants, and green tea extract on hepatic warm IRI in pigs. Methods. pONS (70 g per serving, Fresenius Kabi, Germany) was dissolved in 250 mL tap water and given to pigs 24, 12, and 2 hrs before warm ischemia of the liver. A fourth dose was given 3 hrs after reperfusion. Controls were given the same amount of cellulose with the same volume of water. Two hours after the third dose of pONS, both the portal vein and the hepatic artery were clamped for 40 min. 0.5, 3, 6, and 8 hrs after reperfusion, heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), portal venous flow (PVF), hepatic arterial flow (HAF), bile flow, and transaminases were measured. Liver tissue was taken 8 hrs after reperfusion for histology and immunohistochemistry. Results. HR, MAP, CVP, HAF, and PVF were comparable between the two groups. pONS significantly increased bile flow 8 hrs after reperfusion. ALT and AST were significantly lower after pONS. Histology showed significantly more severe necrosis and neutrophil infiltration in controls. pONS significantly decreased the index of immunohistochemical expression for TNF-α, MPO, and cleaved caspase-3 (P < 0.001). Conclusion. Administration of pONS before and after tissue damage protects the liver from warm IRI via mechanisms including decreasing oxidative stress, lipid peroxidation, apoptosis, and necrosis.

18.
Ann Transplant ; 17(2): 101-10, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22743728

RESUMEN

Experimental animal research has been pivotal in the development of clinical liver transplantation (LTx). Results obtained in these experiments have been applied in clinic and clinical challenges have been scrutinized in animal laboratories. Porcine model is an optimal model in the field of experimental LTx research. Here, we present the various techniques of experimental LTx in the porcine model in detail. Different methods and modifications have been described. The following major steps have been discussed in detail: donor liver preparation, recipient operation including recipient hepatectomy, and reconstruction phase, including the reconstruction of suprahepatic inferior vena cava (SHIVC), portal vein (PV), infrahepatic inferior vena cava (IHIVC), hepatic artery (HA) and bile duct (BD). IHIVC and SHIVC are anastomosed end to end directly or with the use of prosthesis anastomosed side to side. The PV anastomosis is performed end to end between donor and recipient PV, Cuff method or Stump method. Arterialization has been accomplished via carrel patch or donor HA end to end with recipient HA. There are three major methods for reconstruction of BD: end to end or end to side choledochocholedochostomy or choledojejunostomy with Roux-en-Y jejunal loop. Each method has advantages and disadvantages regarding the objectives of the study; the most physiological techniques may be preferred for long-term survival studies, while the faster techniques may be selected for experimentations aiming the direct postoperative phase.


Asunto(s)
Anastomosis Quirúrgica/métodos , Trasplante de Hígado/métodos , Animales , Arteria Hepática/cirugía , Modelos Animales , Vena Porta/cirugía , Porcinos , Trasplante Homólogo/métodos , Vena Cava Inferior/cirugía
19.
J Surg Res ; 171(2): 709-18, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21962811

RESUMEN

Because of anatomical and physiological similarities to humans, porcine small bowel transplantation (SBTx) can be used as an appropriate experimental model in the field of surgical research. Various approaches to SBTx have been described in literature. The aim of this work is to present a review of different surgical techniques of SBTx which have been developed using the porcine model. Our analysis of Medline-cited studies dealing with different techniques of SBTx in porcine models was particularly focused on surgical aspects. With regard to graft procurement and enterectomy, the reported techniques vary widely. Arterial reconstruction is mainly conducted by performing the anastomosis between the superior mesenteric artery (SMA) of the donor and SMA or infrarenal aorta of the recipient. Alternatively, an aortic segment of the donor can be anastomosed to the infrarenal aorta of the recipient. Venous anastomosis is frequently performed between the superior mesenteric vein (SMV) of the donor and SMV or the inferior vena cava (IVC) of the recipient. Some studies also report venous anastomosis between the portal vein of the donor and the recipient. Bowel continuity is then restored by end-to-end or end-to-side anastomosis. Remarkable results were generated thanks to improved techniques which include proximal side-to-side ileo-ileal anastomosis with double-barrel ileostomy, or so-called "Paul-Mikulicz-Ileostomy". Most frequently used were jejunostomy and the "Bishop-Koop-Ileostomy"--where the proximal part of the bowel is anastomosed end-to-side to the distal part, which is then exteriorized as an ostomy. Based on the techniques presented in this review, one must select the most suitable surgical technique of porcine SBTx among those various models.


Asunto(s)
Intestino Delgado/trasplante , Modelos Animales , Trasplante de Órganos/métodos , Porcinos , Anastomosis Quirúrgica/métodos , Animales
20.
Mol Nutr Food Res ; 55(6): 855-63, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21595017

RESUMEN

SCOPE: Polyphenolic constituents of green tea (Camellia sinensis) have been shown to be potent scavengers of reactive oxygen species (ROS). Thus, this study was designed to assess its effects after liver ischemia-reperfusion. METHODS AND RESULTS: Fasted Sprague-Dawley rats were gavaged with different concentrations of green tea extract (GTE) 2 h before 90 min of warm ischemia of the left lateral liver lobe (30% of liver). Controls were given the same volume of Ringer's solution. A preparation of pentobarbital sodium (intraperitoneal) and ketamine (intramuscular) was used for anesthesia. After reperfusion, transaminases, liver histology, hepatic microcirculation, and both phagocytosis of latex bead particles as well as the expression of tumor necrosis alpha (TNF-α) to index cellular activation were investigated. Furthermore, the expression of superoxide dismutase (Mn-SOD) was assessed. After 90 min of warm ischemia aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) increased dramatically to 1946 ± 272/3244 ± 757 U/L, 1680 ± 134/2080 ± 379 U/L, and 7857 ± 1851/2036 ± 1193 U/L at 2/6 h, respectively. GTE (200 mg/kgbody weight) significantly prevented this increase in a dose-dependent manner by 21-51% at 2 h and 29-34% at 6 h, respectively. Histology confirmed the protective effects while both TNF-α expression and phagocytosis of latex beads by Kupffer cells (KCs) were significantly reduced. GTE intake significantly increased the expression of manganese superoxide dismutase. In vivo microscopy revealed improved acinar and sinusoidal perfusion after GTE. CONCLUSION: Preconditioning with a single oral dose of GTE ameliorates ischemia-reperfusion injury in liver. Decreased cellular activation and improved microcirculation are the proposed mechanisms.


Asunto(s)
Depuradores de Radicales Libres/administración & dosificación , Precondicionamiento Isquémico , Hígado/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Daño por Reperfusión/prevención & control , Té/química , Isquemia Tibia/efectos adversos , Animales , Camellia sinensis/química , Relación Dosis-Respuesta a Droga , Femenino , Depuradores de Radicales Libres/uso terapéutico , Macrófagos del Hígado/efectos de los fármacos , Macrófagos del Hígado/patología , Hígado/irrigación sanguínea , Hígado/metabolismo , Hígado/patología , Microcirculación/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/efectos de los fármacos , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
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