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1.
Am J Transplant ; 16(10): 2816-2835, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27273869

RESUMEN

The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.


Asunto(s)
Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Isoanticuerpos/inmunología , Trasplante de Hígado/efectos adversos , Aloinjertos , Humanos , Informe de Investigación
2.
Br J Cancer ; 111(3): 470-6, 2014 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-25072303

RESUMEN

BACKGROUND: Pathological response (PR) to preoperative chemotherapy for colorectal liver metastases (CLM) is recognised as a prognostic factor of outcome. However, the optimal system to assess this parameter is still debated. This study focuses on current methods and proposes a possibly better method for assessing PR. METHODS: Among 223 patients resected for CLM between 2004 and 2011, after more than three cycles of chemotherapy, the percentage of tumour cells, necrosis and fibrosis, and the tumour regression grade were assessed for each of 802 nodules. Pathological response was evaluated according to validated methods and their combinations. A new method combined the percentage of tumour cells and the size of all nodules as follows: , where n is each separate nodule, % is the percentage of remaining tumour cells within nodule n (%) and s is the size of nodule n (cm).The prognostic value of each method was calculated. RESULTS: After a median follow-up of 47 months (3-106), the cumulative 5-year overall survival rate after liver resection was 59%. The proposed method categorised as follows: 0 residual tumour; 0.1-6-cm residual tumour; >6-cm residual tumour, and necrosis rate >50% stratified prognosis (P=0.0027; P=0.02), while the other methods did not. At multivariate analysis, our method remained an independent predictor of outcome (P=0.001). CONCLUSIONS: Combining the percentage of tumour cells multiplied by the size of each separate tumour seems to be a better method for assessing PR. External validation is required.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Bevacizumab , Cetuximab , Estudios de Cohortes , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Terapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Resultado del Tratamiento
3.
Am J Transplant ; 13(11): 2966-77, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24011021

RESUMEN

Plasma cell hepatitis (PCH), also known as "de novo autoimmune" hepatitis, is an increasingly recognized, but suboptimally named and poorly understood, category of late allograft dysfunction strongly resembling autoimmune hepatitis (AIH): They share plasma-cell-rich necro-inflammatory activity on biopsy, autoantibodies and steroid responsiveness, but overlap with rejection is problematic. A retrospective study of clinical, serological, histopathological and IgG4 immunohistological features of PCH (n = 20) in liver allograft recipients, native liver AIH (n = 19) and plasma-cell-rich renal allograft rejection (n = 20) showed: (1) high frequency (44%) of HLA-DR15; (2) less female predominance (p = 0.03) and (3) n = 9/20 PCH recipients showed >25 IgG4+ plasma cells/high-power field (IgG4+ PCH) versus AIH (n = 1/19, p = 0.008) or plasma-cell-rich kidney rejection (n = 2/20, p = 0.03). The IgG4+ PCH (n = 9) subgroup showed lower alanine transaminase (ALT) (p < 0.01) and aspartate transaminase (AST) (p < 0.05) at index biopsy but (a) higher plasma cell number/percentage, (b) more aggressive-appearing portal/periportal and perivenular necro-inflammatory activity and (c) more severe portal/periportal fibrosis than IgG4- PCH (n = 11). Significant demographic, histopathologic and plasma cell phenotype differences between PCH and AIH suggest distinct pathogenic mechanisms for at least the IgG4+ PCH subgroup likely representing an overlap between allo- and auto-immunity. IgG4+ PCH was associated with fibrosis, but also highly responsive to increased immunosuppression.


Asunto(s)
Hepatitis C/patología , Hepatitis Autoinmune/patología , Inmunoglobulina G/inmunología , Trasplante de Hígado/efectos adversos , Células Plasmáticas/patología , Complicaciones Posoperatorias , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Femenino , Estudios de Seguimiento , Factores de Transcripción Forkhead/metabolismo , Hepacivirus/aislamiento & purificación , Hepatitis C/inmunología , Hepatitis C/virología , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/virología , Humanos , Técnicas para Inmunoenzimas , Inmunoglobulina G/metabolismo , Hepatopatías/inmunología , Hepatopatías/cirugía , Hepatopatías/virología , Masculino , Persona de Mediana Edad , Células Plasmáticas/inmunología , Células Plasmáticas/virología , Pronóstico , Estudios Retrospectivos , Adulto Joven
4.
Am J Transplant ; 11(8): 1686-95, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21749638

RESUMEN

We characterized fibrosing cholestatic hepatitis (FCH) in a large cohort of HIV/HCV co-infected patients. Between 1999 and 2008, 59 HIV infected patients were transplanted for end-stage liver disease due to HCV. Eleven patients (19%) developed FCH within a mean period of 7 months [2-27] after liver transplantation (LT). At Week 1 post-LT, the mean HCV viral load was higher in the FCH group: 6.13 log(10) IU/mL ± 1.30 versus 4.9 log(10) IU/mL ± 1.78 in the non-FCH group, p = 0.05. At the onset of acute hepatitis after LT, activity was moderate to severe in 8/11 HIV+/HCV+ patients with FCH (73%) versus 13/28 (46%) HIV+/HCV+ non-FCH (p = 0.007) patients. A complete virological response to anti-HCV therapy was observed in 2/11 (18%) patients. Survival differed significantly between the two groups (at 3 years, 67% in non-FCH patients versus 15% in FCH patients, p = 0.004). An early diagnosis of FCH may be suggested by the presence of marked disease activity when acute hepatitis is diagnosed and when a high viral load is present. The initiation of anti-HCV therapy should be considered at this point.


Asunto(s)
Biomarcadores/sangre , Infecciones por VIH/sangre , Hepatitis C/cirugía , Trasplante de Hígado , Adulto , Anciano , Colestasis Intrahepática , Estudios de Cohortes , Femenino , Infecciones por VIH/complicaciones , Hepatitis C/sangre , Hepatitis C/complicaciones , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Carga Viral
5.
Br J Surg ; 98(3): 399-407, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21254017

RESUMEN

BACKGROUND: The impact of bevacizumab on functional recovery and histology of the liver was evaluated in patients undergoing hepatic resection for colorectal liver metastases (CLM) following bevacizumab treatment. METHODS: Consecutive patients who had resection of CLM between July 2005 and July 2009 following preoperative chemotherapy were identified retrospectively from a prospectively collected database. Patients who had received bevacizumab before the last chemotherapy line were excluded. Postoperative liver function and histology were compared between patients with and without bevacizumab treatment. Recorded parameters included serum prothrombin time, total bilirubin concentration, and levels of aspartate and alanine aminotransferase and γ-glutamyltransferase. RESULTS: Of 208 patients identified, 67 had received last-line bevacizumab, 44 were excluded and 97 had not received bevacizumab. Most patients in the bevacizumab group (66 per cent) received a single line of chemotherapy. Bevacizumab was most often combined with 5-flurouracil/leucovorin and irinotecan (68 per cent). The median number of bevacizumab cycles was 8·6 (range 1-34). Bevacizumab administration was stopped a median of 8 (range 3-19) weeks before surgery. There were no deaths. Postoperative morbidity occurred in 43 and 36 per cent of patients in the bevacizumab and no-bevacizumab groups respectively (P = 0·353). The mean(s.d.) degree of tumour necrosis was significantly higher in the bevacizumab group (55(27) versus 32(29) per cent; P = 0·001). Complete pathological response rates were comparable (3 versus 8 per cent; P = 0·307). Postoperative changes in functional parameters and objective signs of hepatic toxicity were similar in both groups. CONCLUSION: Preoperative administration of bevacizumab does not seem to affect functional recovery of the liver after resection of CLM. Tumour necrosis is increased following bevacizumab treatment.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Neoplasias Colorrectales , Neoplasias Hepáticas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab , Bilirrubina/metabolismo , Femenino , Hepatectomía/métodos , Hepatectomía/mortalidad , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/mortalidad , Protrombina/metabolismo , Recuperación de la Función
6.
Eur J Cancer ; 95: 1-10, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29579478

RESUMEN

BACKGROUND: Resection of breast cancer liver metastases (BCLM) combined with systemic treatment is increasingly accepted but not offered as therapeutic option. New evidence of the additional value of surgery in these patients is scarce while prognoses without surgery remains poor. PATIENTS AND METHODS: For this case matched analysis, all nationally registered patients with BCLM confined to the liver in the Netherlands (systemic group; N = 523) were selected and compared with patients who received systemic treatment and underwent hepatectomy (resection group; N = 139) at a hepatobiliary centre in France. Matching was based on age, decade when diagnosed, interval to metastases, maximum metastases size, single or multiple tumours, chemotherapy, hormonal or targeted therapy after diagnosis. Based on published guidelines, palliative systemic treatment strategies are similar in both European countries. RESULTS: Between 1983 and 2013, 3894 patients were screened for inclusion. Overall median follow-up was 80 months (95% CI 70-90 months). The median, 3- and 5-year overall survival of the whole population was 19 months, 29% and 19%, respectively. The resection and systemic group had median survival of 73 vs. 13 months (P < 0.001), respectively. Three and 5-year survival was 18% and 10% for the systemic group and 75% and 54% for the resection group, respectively. After matching, the resection group had a median overall survival of 82 months with a 3- and 5-year overall survival of 81% and 69%, respectively, compared with a median overall survival of 31 months in the systemic group with a 3- and 5-year overall survival of 32% and 24%, respectively (HR 0.28, 95% CI 0.15-0.52; P < 0.001). CONCLUSIONS: For patients with BCLM, liver resection combined with systemic treatment results in improved overall survival compared to systemic treatment alone. Liver resection should be considered in selected cases.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Europa (Continente)/epidemiología , Femenino , Francia/epidemiología , Hepatectomía/estadística & datos numéricos , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Países Bajos/epidemiología , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
7.
J Visc Surg ; 155(4): 265-273, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29525540

RESUMEN

BACKGROUND: Hepatectomy remains the standard treatment for large hepatocellular carcinoma (LHCC) ≥5cm. Fibrosis may constitute a contraindication for resection because of high risk of post-hepatectomy liver failure, but its impact on patient outcome and cancer recurrence remains ill defined. Our aim was to compare predictors of survival in patients with and without cirrhosis following hepatectomy for LHCC. METHODS: The data on consecutive patients undergoing hepatectomy for LHCC in two tertiary centres between 2012 and 2016 were reviewed. The outcomes of cirrhotic (F4) and non-cirrhotic (F0-F3) patients were compared. Patients with perioperative medical (sorafenib) or radiological (transarterial chemoembolization, radiofrequency) treatments were excluded. RESULTS: Sixty patients were included. Preoperative and intraoperative features were identical between both groups. Cirrhotics (n=15) presented more satellite nodules on specimens (73% vs. 44%; P=0.073) but better differentiated lesions than non-cirrhotics (P=0.041). The median overall survival of cirrhotics was 34 vs. 29months for non-cirrhotics (P=0.8), and their disease-free survival was 14 versus 18 months (P=0.9). Fibrosis stage did not impact overall (P=0.2) nor disease-free survivals (P=0.6). CONCLUSION: Hepatectomy for LHCC in cirrhotics can achieve acceptable oncological results when compared to non-cirrhotic patients. Curative resection of LHCC should be attempted if liver function is acceptable, whatever the fibrosis stage.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía/mortalidad , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/cirugía , Anciano , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Carga Tumoral
8.
J Visc Surg ; 154(5): 345-353, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28844704

RESUMEN

Gallbladder (GB) adenomyomatosis (ADM) is a benign, acquired anomaly, characterized by hypertrophy of the mucosal epithelium that invaginates into the interstices of a thickened muscularis forming so-called Rokitansky-Aschoff sinuses. There are three forms of ADM: segmental, fundal and more rarely, diffuse. Etiology and pathogenesis are not well understood but chronic inflammation of the GB is a necessary precursor. Prevalence of ADM in cholecystectomy specimens is estimated between 1% and 9% with a balanced sex ratio; the incidence increases after the age of 50. ADM, although usually asymptomatic, can manifest as abdominal pain or hepatic colic, even in the absence of associated gallstones (50% to 90% of cases). ADM can also be revealed by an attack of acalculous cholecystitis. Pre-operative diagnosis is based mainly on ultrasound (US), which identifies intra-parietal pseudo-cystic images and "comet tail" artifacts. MRI with MRI cholangiography sequences is the reference examination with characteristic "pearl necklace" images. Symptomatic ADM is an indication for cholecystectomy, which results in complete disappearance of symptoms. Asymptomatic ADM is not an indication for surgery, but the radiological diagnosis must be beyond any doubt. If there is any diagnostic doubt about the possibility of GB cancer, a cholecystectomy is justified. The discovery of ADM in a cholecystectomy specimen does not require special surveillance.


Asunto(s)
Adenomioma/diagnóstico por imagen , Adenomioma/patología , Colecistectomía/métodos , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/patología , Adenomioma/cirugía , Anciano , Biopsia con Aguja , Colangiografía/métodos , Diagnóstico Diferencial , Femenino , Enfermedades de la Vesícula Biliar/diagnóstico por imagen , Enfermedades de la Vesícula Biliar/patología , Enfermedades de la Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Resultado del Tratamiento
9.
Oncogene ; 13(12): 2681-5, 1996 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-9000142

RESUMEN

The molecular basis of cirrhosis, the most frequent underlying liver disease in hepatocellular carcinoma, remains unclear. We investigated microsatellite instability at six different loci on chromosomes 2p, 3p, 5q, 9p, 13q and 17p, in DNA from 38 cirrhotic livers of viral (n=28) and nonviral (n=10) origin. Sixty percent of the patients exhibited microsatellite alterations in at least one chromosome locus. A striking feature was the close association between genomic instability and cirrhosis linked to hepatitis B viral infection (P<0.01). This high instability may be a clue to the etiology of cancer induced by the hepatitis B virus.


Asunto(s)
Hepatitis B/complicaciones , Cirrosis Hepática/genética , Repeticiones de Microsatélite/genética , Adulto , Anciano , Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 2/genética , Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 5/genética , Cromosomas Humanos Par 9/genética , Femenino , Humanos , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad
10.
Target Oncol ; 10(3): 415-21, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25420993

RESUMEN

Recent data showed that metastatic colorectal (mCRC) tumors exhibiting extended RAS-BRAF mutations were resistant to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, making these drugs suitable for the so-called "super" wild-type (WT) patients only. This study aimed to compare the extended RAS-BRAF mutation frequency and characteristics according to location of tumor sampling. All consecutive mCRC specimens (N = 1659) referred to our institution from January 2008 till June 2014 were included in the analysis. Tumor genotyping (first for KRAS exon 2, then for BRAF exon 15, and later for KRAS exons 2, 3, and 4 and NRAS exons 2, 3, and 4) was performed with high-resolution melting analysis or allelic discrimination. The factors predicting for the presence of mutation were explored using multivariate binary logistic regression. Overall, the prevalence of KRAS exon 2 was 36.8%, and it was lower in liver metastases (N = 138/490; 28.2%) in comparison with primary tumors (N = 442/1086; 40.7%), lung metastases (16/32; 50%), or other metastatic sites (15/51; 29.4%; P < 0.0001). Similarly, in the 1428 samples analyzed, BRAF mutations were less often found in liver metastases (N = 9/396; 2.3%) as compared to primary tumors (N = 79/959; 8.2%), lung metastases (N = 2/29; 6.9%), or other metastatic locations (N = 2/44; 4.5%; P < 0.0002). Overall occurrence of extended RAS mutation was 51.7%. Of the 503 samples tested, the prevalence of extended RAS-BRAF mutations was twice as low in liver metastases (N = 53/151; 34.2 %) as compared to primary tumors (N = 191/322; 59.3%, P < 0.0001). Univariate analysis identified age ≤65 years, male gender, and liver localization as predictors of super WT status. At multivariate analysis, only liver metastases were retained (RR 2.85 [95% CI 1.91-4.30]). Colorectal liver metastases are twice as likely to exhibit a super WT genotype as compared to other tumor locations independently from other factors. This molecular feature has the potential to influence therapeutic strategy in mCRC patients.


Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Mutación , Anciano , Análisis Mutacional de ADN , Exones , Femenino , GTP Fosfohidrolasas/genética , Genotipo , Humanos , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Prevalencia , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Análisis de Regresión , Transducción de Señal
11.
Am J Surg Pathol ; 19(1): 81-90, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7802140

RESUMEN

Sclerosing cholangitis defined by cholangiographic criteria may occur after orthotopic liver transplantation. In this retrospective study, we analyzed failed grafts and antecedent serial biopsies of 24 patients who developed this type of nonanastomotic biliary strictures. Sclerosing cholangitis was histologically diagnosed if there was a combination of periductal fibrosis and features of large bile duct obstruction. The condition was observed in all but one available failed allografts. This later showed ischemic-type lesions without periductal fibrosis. Liver biopsy specimens were nondiagnostic relative to sclerosing cholangitis, although 85% of the patients had evidence of large bile duct obstruction. Numerous associated factors may explain the pathogenesis of secondary sclerosing cholangitis: an immunologically related etiologic factor (10 recipients of ABO-incompatible allografts) and compromised arterial blood flow that likely resulted from hepatic artery thrombosis (12 patients), focal arterial fibrointimal hyperplasia (three patients), chronic ductopenic arteriopathic rejection (three patients) and/or preservation-related ischemia (four patients). Sclerosing cholangitis may be a significant cause of graft failure that often has misleading biopsy manifestations. From a practical standpoint, cholestasis with evidence of large bile duct obstruction warrants cholangiographic assessment of the biliary tree.


Asunto(s)
Colangitis Esclerosante/etiología , Trasplante de Hígado , Complicaciones Posoperatorias , Adolescente , Adulto , Conductos Biliares/patología , Biopsia , Colangiografía , Colangitis Esclerosante/patología , Femenino , Rechazo de Injerto , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Factores de Tiempo
12.
Transplantation ; 65(8): 1072-5, 1998 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-9583868

RESUMEN

BACKGROUND: The precise immunologic mechanisms responsible for chronic rejection of liver allografts are unknown. We have recently shown in a rodent model that recipients of liver allografts developed non-major histocompatibility complex antitissue antibodies. The aim of the present study was to test this hypothesis in the clinical setting. METHODS: Posttransplant sera of 14 patients undergoing chronic rejection and of 48 control patients (12 liver transplant patients with chronic active hepatitis or liver cirrhosis related to hepatitis C virus [HCV] infection and without chronic rejection, 10 with sclerosing cholangitis, and 26 with normal liver function tests and liver biopsy) were tested for the presence of antitissue antibodies by indirect immunofluorescence. Pretransplant sera of all these patients lacked antitissue antibodies. RESULTS: Antitissue antibodies were detected in 71% of patients who developed chronic rejection (before or at the time of chronic rejection). This incidence was significantly greater than that observed in patients not undergoing rejection (HCV-related chronic active hepatitis, 16%; sclerosing cholangitis, 0%; normal liver biopsy, 7%). All these autoantibodies were directed against the smooth muscle and/or the nucleus. In two patients, anti-smooth muscle antibodies had an antiactin or antivimentin specificity. CONCLUSIONS: These results show a strong association between chronic allograft rejection and the development of antitissue antibodies and suggest that these antibodies could be used to identify patients at high risk of developing chronic rejection after liver transplantation.


Asunto(s)
Autoanticuerpos/sangre , Rechazo de Injerto/inmunología , Hepatitis C/inmunología , Isoanticuerpos/sangre , Cirrosis Hepática/inmunología , Trasplante de Hígado/inmunología , Formación de Anticuerpos , Colangitis Esclerosante/sangre , Colangitis Esclerosante/inmunología , Enfermedad Crónica , Técnica del Anticuerpo Fluorescente , Estudios de Seguimiento , Rechazo de Injerto/sangre , Hepatitis C/sangre , Humanos , Cirrosis Hepática/sangre , Pruebas de Función Hepática , Trasplante de Hígado/patología , Trasplante de Hígado/fisiología , Estudios Retrospectivos , Factores de Tiempo , Trasplante Homólogo
13.
Transplantation ; 65(10): 1328-33, 1998 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-9625014

RESUMEN

BACKGROUND: Recurrence of primary biliary cirrhosis (PBC) within liver allografts remains a controversial issue. The aims of this study were to evaluate this risk and to determine the presence, if any, of a predictive histological feature. METHODS: We reviewed the most recent and the 1-year protocol liver biopsies of 69 patients who received transplants for PBC and of 53 control patients. Histological features consistent with PBC recurrence included nonsuppurative destructive cholangitis, mixed portal infiltrate, fibrosis, and ductopenia. A complete evaluation was undertaken in each patient with these histological features. RESULTS: These histological features were present in six patients who received transplants for PBC (8.7% vs. 0% in the control group) and occurred between 1 and 8 years after transplant. In five of the six patients, anti-mitochondrial antibody-2 (anti-M2) antibodies remained at high titers. Cholestasis was present in four patients, and clinical symptoms in two patients. All six patients were negative for hepatitis C antibodies and hepatitis C RNA in their serum. None had bile duct obstruction. The presence of plasma cells in the portal infiltrate at 1 year after transplant was predictive of this risk of recurrence. CONCLUSION: The risk of PBC recurrence is real (8.7%). The presence of plasma cells in the portal infiltrate seems to be an early marker of recurrence of PBC in patients transplanted for this indication.


Asunto(s)
Cirrosis Hepática Biliar/cirugía , Trasplante de Hígado , Hígado/patología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Células Plasmáticas/patología , Sistema Porta/patología , Periodo Posoperatorio , Pronóstico , Recurrencia
14.
Transplantation ; 72(3): 393-405, 2001 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-11502966

RESUMEN

BACKGROUND: The clinical development of liver-support devices based on perfusion of either pig hepatocytes cartridges or whole pig livers has been hampered by the ability to use sufficient liver cell mass to provide adequate metabolic support, limited perfusion times, and the potential for patient exposure to pig zoonotic diseases. METHODS: We designed an original system in which an isolated intact pig liver was perfused extracorporeally under physiological conditions in a closed loop circuit with allogeneic pig blood and constant monitoring of major physiological and functional parameters. The perfusion circuit further included an interface membrane to provide for separation of patient and liver perfusion circulation. RESULTS: Prolonged (6-21 hr) liver perfusion did not produce significant liver damage as reflected by modest rises in the levels of the serum transaminases, stability of main biochemical parameters (including potassium), and the maintenance of normal cellular morphology. Optimal liver function was documented as measured by lactate consumption, control of glycemia, and the results of clotting studies and functional assays. The perfused liver cleared 82% and 79% of peak bilirubin and ammonia concentrations with clearing kinetics identical throughout perfusion. Indocyanine green clearance was identical to that observed in the living donor before explant surgery. CONCLUSIONS: In conclusion, the extracorporeal pig liver perfusion apparatus described here allows optimal pig liver function for prolonged periods of time. The microporous membrane to provide separation of donor organ and recipient and the high level of functional activity suggest that this form of liver metabolic support may have important clinical applications.


Asunto(s)
Circulación Extracorporea , Hígado/metabolismo , Amoníaco/sangre , Animales , Arterias , Bilirrubina/orina , Sangre/metabolismo , Factores de Coagulación Sanguínea/biosíntesis , Cuerpos Cetónicos/sangre , Hígado/patología , Hígado/fisiología , Pruebas de Función Hepática , Perfusión/instrumentación , Perfusión/métodos , Biosíntesis de Proteínas , Porcinos , Factores de Tiempo , Urea/metabolismo
15.
Biotechniques ; 15(4): 730-7, 1993 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8251176

RESUMEN

Gene expression studies require a sensitive and quantitative assay of mRNA amounts present in small samples. We describe a general method of quantifying specific mRNA quickly and easily from purified RNA or directly from a few cells by PCR and enzyme-linked immunosorbent assay (ELISA) revelation of the resulting products (sensitivity of the last step: < 0.1 fmol). Cells are digested and the total cellular RNA is reverse-transcribed and then amplified with 5' and 3' primers; the former being 5' biotinylated. The amplification product is captured on avidin-coated microplates and quantified by hybridization with a digoxigenin-labeled internal oligonucleotide probe. After revelation with an anti-digoxigenin alkaline phosphatase coupled antibody (anti-DIG-AP1), the amount of hybridized probe is determined by optical reading. The results can be easily converted to absolute values by comparison with an external DNA standard curve. An internal DNA or RNA standard can also be used. The method we describe can be adapted to any cellular or viral gene of known sequence in a matter of days. Since it uses nonradioactive probes, commercially available reagents and standard microplate readers, it is inexpensive and could be automated easily. In this study, interleukin-2 mRNA expression could be studied in as few as 40 Jurkat cells. It was also possible to quantify human immunodeficiency virus (HIV) DNA from 1500 to 1.5 copies out of 1.5 x 10(5) human genomic DNA copies.


Asunto(s)
Ensayo de Inmunoadsorción Enzimática , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Avidina , Secuencia de Bases , Biotina , Línea Celular , ADN Viral/análisis , Digoxigenina , VIH/genética , Interleucina-2/genética , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Sondas de Oligonucleótidos
16.
Hum Pathol ; 24(10): 1095-7, 1993 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8406419

RESUMEN

We examined surgical liver specimens from 52 patients with hepatitis C virus-related cirrhosis. All patients underwent orthotopic liver transplantation at Paul Brousse Hospital. They were found to be seropositive for antibodies to hepatitis C virus by second-generation testing (RIBA 2, Ortho Diagnostic Systems Inc, Westwood, MA). We detected multiple granulomas in five (10%) of the cirrhotic livers. These granulomas were composed of epithelioid cells, sometimes associated with multinucleated giant cells, and were surrounded by small lymphocytes and fibrosis. The epithelioid granulomas were located within the cirrhotic nodules. They were not present within the portal tracts or within the fibrosis. These granulomas were diffusely distributed in the liver. None of the patients with diffuse hepatic epithelioid granulomas had evidence of tuberculosis or brucellosis before transplantation or during the follow-up period (range, 3 to 20 months). They had no detectable cause of granulomatous hepatitis. The role of hepatitis C virus as a cause of epithelioid granulomas is discussed.


Asunto(s)
Granuloma/patología , Hepatitis C/patología , Cirrosis Hepática/patología , Adulto , Femenino , Hepatitis C/complicaciones , Humanos , Cirrosis Hepática/etiología , Trasplante de Hígado , Masculino , Persona de Mediana Edad
17.
Surgery ; 117(2): 146-55, 1995 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7846618

RESUMEN

BACKGROUND: Little information is available on the indications for, and the efficacy and timing of, liver transplantation in patients with primary sclerosing cholangitis (PSC). This issue is particularly relevant because prolonged survival has been reported in patients who do not undergo transplantation. METHODS: Long-term results of therapeutic interventions including liver transplantation was assessed in a representative series of 51 patients. Patient survival was compared with that expected from prognostic models. RESULTS: Actuarial symptom-free survival rate in patients treated by nontransplantation biliary surgery (n = 23) was 35% at 10 years. Actuarial survival rate from onset of PSC (56% at 10 years) was identical to that expected from the prognostic model. Actuarial patient (n = 28) survival rate 5 years after transplantation was greater than that expected from prognostic models (89% versus 31%; p < 0.001). Previous abdominal surgery was associated with an increased in-hospital mortality rate (p < 0.05). Cumulative actuarial incidence of cancer 5 and 10 years after the onset of PSC was 13% and 31%, respectively. CONCLUSIONS: Liver transplantation improves the prognosis of patients with PSC. Failure to identify patients who will benefit from nontransplantation therapeutic interventions or in whom a cancer will develop, and the risk associated with previous abdominal surgery, suggest that liver transplantation should be indicated early after onset of symptoms.


Asunto(s)
Colangitis Esclerosante/mortalidad , Colangitis Esclerosante/cirugía , Trasplante de Hígado , Adulto , Neoplasias de los Conductos Biliares/epidemiología , Procedimientos Quirúrgicos del Sistema Biliar , Transfusión Sanguínea/estadística & datos numéricos , Supervivencia sin Enfermedad , Drenaje , Femenino , Estudios de Seguimiento , Humanos , Cuidados Intraoperatorios , Neoplasias Hepáticas/epidemiología , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
18.
Gastroenterol Clin Biol ; 23(2): 264-7, 1999 Feb.
Artículo en Francés | MEDLINE | ID: mdl-10353020

RESUMEN

Liver disease is a rare complication of pregnancy which can be serious for both the mother and the infant. In particular, HELLP syndrome (hemolysis, elevated liver enzymes and a low platelet count) is a life threatening complication of severe preeclampsia. Pregnancies complicated by the HELLP syndrome are usually associated with increased maternal and perinatal morbidity and mortality including disseminated intravascular coagulopathy, pulmonary and cerebral oedema, acute renal failure, rupture of the liver hematoma and a variety of hemorrhagic complications. The HELLP syndrome occurs in 4 to 12% of patients with severe preeclampsia and prompt delivery is the only treatment. We report two cases of HELLP syndrome which developed in women during delivery and without any predictive factors during pregnancy.


Asunto(s)
Síndrome HELLP/complicaciones , Complicaciones del Trabajo de Parto , Preeclampsia/complicaciones , Adulto , Femenino , Humanos , Embarazo , Pronóstico
19.
Ann Pathol ; 20(4): 304-7, 2000 Sep.
Artículo en Francés | MEDLINE | ID: mdl-11015647

RESUMEN

Our aim was to evaluate the clinical impact of pathology review in an oncology center, in which review is not performed for every patient. This retrospective study involved 100 consecutive patients, whose slides were reviewed in our center. A standardized data sheet was filled out by oncologists for each patient. Pathology review was considered as responsible for a major (35%), moderate (40%), or mild or no (25%) modification of clinical practice. Modification concerned either initial investigations, treatment or medical follow up, and was independent of the reason for which review was performed. Eleven patients underwent a second biopsy. Whatever the possible discrepancies between initial and review diagnosis, our results show that pathological review has a major influence on clinical practice in patients with cancer.


Asunto(s)
Neoplasias/patología , Neoplasias/terapia , Patología/normas , Humanos , Variaciones Dependientes del Observador , Control de Calidad , Estudios Retrospectivos
20.
Ann Otolaryngol Chir Cervicofac ; 121(3): 156-60, 2004 Jun.
Artículo en Francés | MEDLINE | ID: mdl-15224001

RESUMEN

OBJECTIVES: When tracheal stenosis is symptomatic, the treatment may consist of surgical resection and anastomosis. A multifilament absorbable suture is usually used. The aim of this experimental work on rats was to study the benefits of using a monofilament absorbable suture with high initial resistance. MATERIAL AND METHODS: We compared Ethilon, a nylon monofilament non-absorbable suture (MNA), with Monocryl, a polyglecaprone 25 (P25) monofilament absorbable suture (MA). The sutures were used for tracheal anastomosis on 16 rats. P25 has a high initial strength but its intra-tissular disappearance is fast. Animals were killed at 1, 2 and 3 months. Anastomoses were studied by optical microscopy and histological analysis. RESULTS: At 3 months no disunity or stenosis was seen with the MA. With the MNA, a modification of the tracheal transverse section and a stenosis were observed. The histological examination showed an initial important inflammatory cell reaction with the MA and at 3 months, a surgery-free like tracheal aspect. At 3 months the rats with MNA had a persistent foreign body cell reaction. CONCLUSION: Good results obtained by using P25 could be due to high initial resistance of the suture protecting the anastomosis. The semi-fast absorption of the suture avoided persistent inflammatory cell reaction. Confirmation of these results by working on larger animals and tracheal anastomosis under tension could allow the use of this suture on human beings, in this instance.


Asunto(s)
Suturas/clasificación , Estenosis Traqueal/cirugía , Adsorción , Anastomosis Quirúrgica/métodos , Animales , Dioxanos/uso terapéutico , Femenino , Poliésteres/uso terapéutico , Ratas , Ratas Wistar , Estenosis Traqueal/patología
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