RESUMEN
BACKGROUND: Long-term results after downstaging hepatocellular carcinoma (HCC) prior to liver transplantation (LT) remain unknown. AIMS: To investigate dropouts and post-transplant outcome among patients with downstaged HCC by transarterial chemo-lipiodolization (TACL). METHODS: Between 2000 and 2007, 386 patients with HCC initially exceeding Milan criteria underwent TACL for tumour downstaging and were consecutively enrolled. RESULTS: Overall, 160 (41.5%) patients achieved successful downstaging of HCC to within Milan criteria. During the follow-up, 82 eventually dropped off the waiting list for LT, with estimated dropout rates at 1, 2 and 5 years of 46.7%, 70.2%, and 87.2%, respectively. The overall post-transplant survival rates at 1, 2 and 5 years were 89.2%, 70.3% and 54.6% and the corresponding rates for recurrence-free survival were 74.7%, 71.8% and 66.3% respectively. Multivariate analysis indentified alpha-fetoprotein (AFP) levels > or = 100 ng/mL at LT (P = 0.003), maximum tumour size > or = 7 cm (P = 0.002) and the lack of complete necrosis by TACL (P = 0.048) as independent predictors of HCC recurrence after LT. Patients with none of these risk factors had an excellent post-transplant outcome, with an 87.5% probability of recurrence-free survival up to 6 years. CONCLUSIONS: These long-term results may contribute to the database for optimizing management of LT candidates with downstaged HCC. Based on our data, patients with a maximum tumour size <7 cm who achieve complete necrosis together with AFP levels <100 ng/mL at LT may be the best candidates for LT following downstaging using TACL.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Estadificación de Neoplasias/métodos , Cuidados Preoperatorios/métodos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Selección de Paciente , Tasa de Supervivencia , Listas de EsperaRESUMEN
Interferon-alpha (IFN-alpha) has been reported to be beneficial in the treatment of chronic active hepatitis occurring as a result of hepatitis B virus (HBV) infection. Treatment with IFN-alpha has been proposed as a means of reducing the high rate of allograft infection in clinical liver transplantation in patients transplanted for HBV-related chronic active hepatitis and cirrhosis who are positive for hepatitis B surface antigen (HBsAg). We obtained resected whole livers from two groups of patients who received liver transplants. Group A consisted of 11 patients who were HBsAg+ but were not treated with IFN-alpha, and group B consisted of 10 patients who were also HBsAg+ but received IFN-alpha therapy for 29.4 +/- 5.6 days prior to orthotopic liver transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. The liver tissue was stained with monoclonal antibodies to cell surface antigens unique to different mononuclear cell populations by the avidin-biotin-immunoperoxidase technique to determine the effect of IFN-alpha on the lymphocyte subsets as well as HLA antigen expression on liver-infiltrating mononuclear cells. The number of HLA-DR+ lymphocytes in the liver was significantly increased (P less than 0.005) within the portal areas in group B compared with that found in group A (84 +/- 14 versus 33 +/- 5 per one high-power field). Moreover, the intensity of the HLA-DR antigen expression on lymphocytes in the portal areas (P less than 0.02) and in the hepatic lobule (P less than 0.05) was greater in group B than in group A. The number of natural killer (NK) cells was increased in the portal areas (P less than 0.05) of group B compared with group A. These alterations in the lymphocyte and NK cell populations present in the liver in response to IFN-alpha therapy presumably reflect an IFN-alpha-induced enhancement of the immune response to virus-infected cells.
Asunto(s)
Antígenos HLA-DR/metabolismo , Hepatitis B/inmunología , Interferón Tipo I/farmacología , Hígado/inmunología , Subgrupos Linfocitarios/inmunología , Adulto , Distribución de Chi-Cuadrado , Femenino , Hepatitis B/complicaciones , Hepatitis B/patología , Antígenos de Superficie de la Hepatitis B/análisis , Hepatitis Crónica/complicaciones , Hepatitis Crónica/inmunología , Hepatitis Crónica/patología , Humanos , Células Asesinas Naturales/inmunología , Hígado/patología , Cirrosis Hepática/etiología , Cirrosis Hepática/inmunología , Cirrosis Hepática/patología , Subgrupos Linfocitarios/patología , Masculino , Persona de Mediana Edad , Proteínas RecombinantesRESUMEN
A bloody nasogastric aspirate is believed to imply active upper gastrointestinal tract bleeding, while a nonbloody yellow-green nasogastric aspirate that contains duodenal secretions suggests the absence of bleeding proximal to the ligament of Treitz. To validate these beliefs, physicians were asked to predict the presence of active gastrointestinal tract bleeding and whether bile was present in a nasogastric aspirate obtained immediately before endoscopy in 73 episodes of bleeding in 62 patients. A relationship was found between the physician's assessment of the presence of active bleeding demonstrated endoscopically and the appearance of the nasogastric aspirate. However, the sensitivity and specificity were low (79% and 55%, respectively). No association between the assessment of bile in the nasogastric aspirate and the presence of bile acids was demonstrated. These data do not support the placement of a nasogastric tube to determine whether or not a patient is bleeding, the location of the bleeding, and whether endoscopy should be performed.
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Hemorragia Gastrointestinal/diagnóstico , Intubación Gastrointestinal/métodos , Succión/métodos , Bilis/análisis , Endoscopía , Femenino , Hemorragia Gastrointestinal/epidemiología , Humanos , Incidencia , Masculino , Sangre Oculta , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
Upper gastrointestinal hemorrhage is one of the more important complications of cirrhosis and a major cause of death in such patients. The main sites of bleeding are esophageal varices, gastritis, and peptic ulcers. In order to determine the prevalence of either potential bleeding lesions or of other endoscopic findings in hemodynamically stable individuals with various etiologies of cirrhosis, 510 consecutive cirrhotic patients, evaluated for possible orthotopic liver transplantation (OLTx) underwent an upper gastrointestinal endoscopy for combined diagnostic and therapeutic purposes. The patients were divided into two main groups: 319 patients with parenchymal liver disease and 191 patients with cholestatic liver disease. Gastritis was found significantly more often in patients with parenchymal liver disease than in those with cholestatic liver disease (49.8% vs 30.9%; P less than 0.001). In contrast, the prevalence of esophagitis, esophageal and gastric varices, gastric ulcer, duodenal ulcer, and duodenitis was similar in both groups. Normal endoscopic findings were present in 5.0% of the parenchymal group and 11.5% of the cholestatic group (P less than 0.02). Ascites and encephalopathy were found significantly more often in subjects with parenchymal liver disease as compared to those with cholestatic liver disease. Portal hypertension and its degree, as assessed by the presence and size of esophageal varices, was similar in both groups, and in both groups there was a statistically significant qualitative trend of increasing prevalence of esophageal varices with increasing severity of disease as estimated using Pugh-Child's criteria.
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Fibrosis/patología , Colestasis/clasificación , Colestasis/patología , Sistema Digestivo/patología , Endoscopía , Femenino , Gastritis/complicaciones , Humanos , Hepatopatías/clasificación , Hepatopatías/complicaciones , Hepatopatías/patología , Masculino , Estudios ProspectivosRESUMEN
Tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes from 7 patients with adenocarcinoma of the colon were evaluated for expansion and antitumor activities during culture in the presence of 1000 U/ml of recombinant human interleukin 2. Functional and phenotypic characteristics of tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes were compared between weeks 2 and 3 of culture in recombinant interleukin 2. All but one tumor-infiltrating lymphocyte and all autologous peripheral blood lymphocyte preparations proliferated well in vitro. Tumor-infiltrating lymphocytes expanded better (p less than 0.05) than autologous peripheral blood lymphocytes, reaching median-fold expansions of 2231 (range 1-4720) and 108 (range 13-1263), respectively. Cytotoxicity of interleukin 2-activated tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes against fresh autologous or allogeneic colon carcinoma targets was relatively low in these cultures. Due to better proliferation, tumor-infiltrating lymphocytes showed significantly greater (p less than 0.05) total cytotoxic activity per culture against fresh autologous tumor-cell targets than did autologous peripheral blood lymphocytes, achieving a median total lytic units of activity per culture of 671 compared with 92 for autologous peripheral blood lymphocytes. Cytotoxicity was not restricted to autologous tumor cells. Two-color flow cytometry demonstrated that the predominant proliferating cell population in interleukin 2-expanded long-term cultures of tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes expressed the CD3+Leu19- phenotype. Some cultures were enriched in CD3+ Leu19+ and CD3-Leu19+ cells. This study indicated that tumor-infiltrating lymphocytes from most but not all human primary colon adenocarcinomas could be expanded in the presence of recombinant interleukin 2 and mediate non-major histocompatibility complex-restricted antitumor cytotoxicity. Because fresh colon carcinoma cells appear to be resistant to in vitro lysis by interleukin 2-activated tumor-infiltrating lymphocyte and autologous peripheral blood lymphocyte effectors, the role of adoptive immuno-therapy in treatment of advanced colon carcinomas in humans may have to be reevaluated.
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Adenocarcinoma/patología , Neoplasias del Colon/patología , Inmunización Pasiva , Interleucina-2/farmacología , Linfocitos T Citotóxicos/fisiología , Anciano , Anciano de 80 o más Años , Citotoxicidad Inmunológica , Femenino , Citometría de Flujo , Humanos , Linfocitos/fisiología , Masculino , Persona de Mediana Edad , Fenotipo , Proteínas Recombinantes/farmacología , Células Tumorales CultivadasRESUMEN
Several studies performed in alcoholics with advanced liver disease have demonstrated a positive correlation between the serum-ascites albumin gradient (SAAG) and measured portal venous pressure. A single study performed in 15 patients with exudative malignant ascites and 29 patients with alcoholic liver disease demonstrated that a SAAG of less than 1.1 was essentially diagnostic of a malignant origin of the ascites. In an effort to confirm and extend these observations to individuals with nonalcoholic liver disease, 24 patients with nonalcoholic liver disease and 11 with alcoholic liver disease undergoing orthotopic liver transplantation (OTLx) were studied. At the time of liver transplantation, each had their serum and ascitic fluid albumin levels determined, the gradient calculated, and their portal venous pressure (PVP) as well as the corrected portal venous pressure (PPc) measured directly. A significant correlation (r = 0.624) between the PPc and the SAAG was found in the 11 alcoholics (P less than 0.05). No such correlation existed for those with nonalcoholic liver disease (r = 0.398). Moreover, a SAAG less than 1.1 was found in three of nonalcoholics with cirrhosis in the absence of an abdominal malignancy. We conclude that (1) the SAAG and PPc are statistically related to each other in individuals with alcoholic liver disease but not in those with a nonalcoholic cause for cirrhosis, and (2) SAAG less than 1.1 is not diagnostic of abdominal malignancy but can occur in those with advanced nonmalignant hepatic disease.
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Albúminas/análisis , Líquido Ascítico/análisis , Hepatopatías Alcohólicas/metabolismo , Hepatopatías/metabolismo , Albúmina Sérica/análisis , Adulto , Ascitis/etiología , Femenino , Humanos , Hipertensión Portal/diagnóstico , Hepatopatías/diagnóstico , Hepatopatías Alcohólicas/diagnóstico , MasculinoRESUMEN
Alpha-interferon (IFN-alpha) has been shown to be beneficial in the treatment of chronic active hepatitis occurring as a consequence of hepatitis B virus (HBV) infection. Therefore, it has been used to reduce the high rate of allograft infection in clinical liver transplantation of HBV-positive individuals. This study was performed to evaluate the effect of IFN-alpha on lymphocyte subsets as well as the HLA-DR antigen expression in liver tissue. The resected livers obtained from two groups of patients who received liver transplants between 1983 and 1987 at the University of Pittsburgh were examined: group A consisted of 11 patients who were not treated (controls), and group B consisted of 10 patients (experimental group) who were treated with IFN-alpha for 29.4 +/- 5.6 days prior to transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. Both groups had cirrhosis as a result of chronic HBV infection. Monoclonal antibodies to cell-surface antigens unique to different lymphocyte populations and the HLA-DR antigens were used in conjunction with the avidin-biotin-immunoperoxidase technique to identify cells in tissue sections. The number of HLA-DR-positive lymphocytes in the liver was increased (P less than 0.005) within the portal areas in rIFN-alpha-treated group as compared to that seen in the untreated group (84.4 +/- 13.6/HPF vs 33.3 +/- 4.8/HPF). Moreover, the intensity of the HLA-DR antigen expression in the portal areas (P less than 0.02) and in the hepatic lobule (P less than 0.05) was greater in the treated group than in untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Antígenos HLA-DR/análisis , Interferón Tipo I/uso terapéutico , Hígado/efectos de los fármacos , Linfocitos/efectos de los fármacos , Enfermedad Crónica , Femenino , Hepatitis B/inmunología , Hepatitis B/cirugía , Humanos , Células Asesinas Naturales/efectos de los fármacos , Recuento de Leucocitos/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Hígado/inmunología , Hígado/patología , Cirrosis Hepática/inmunología , Cirrosis Hepática/cirugía , Trasplante de Hígado/inmunología , Masculino , Persona de Mediana Edad , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Linfocitos T Reguladores/efectos de los fármacosRESUMEN
The standard procedure for percutaneous liver biopsy (PLB) involves only the use of local anesthesia. However, at times, a PLB can be frightening and uncomfortable. Such experiences often limit the willingness of patients to undergo subsequent follow-up biopsies. To investigate the ability of midazolam, a new water-soluble benzodiazepine preparation, noted for its potency, rapid onset of action, and amnestic qualities, to enhance patient acceptability of a follow-up liver biopsy, a "sedative dose" of midazolam (2 mg) or saline was administered immediately prior to and following a percutaneous liver biopsy. The initial dose was used to sedate the subject while not impairing patient cooperation during the biopsy procedure; the second dose was used to induce amnesia for the biopsy procedure. The next morning patient recollection for the preceding biopsy procedure and their willingness to undergo a future PLB were assessed using a questionnaire. Forty-one patients (ages 18-78) were randomized to receive either midazolam (N = 21) or saline/placebo N = 20) treatment. All PLBs were obtained with a Trucut needle. All subjects were given 2-5 cc of 2% xylocaine local anesthetic at the biopsy site. The questionnaire utilized evaluated patient experience of the procedure with respect to their recall, level of anxiety during the procedure, and willingness to undergo a repeat procedure. The data obtained revealed that those receiving midazolam admitted to experiencing less discomfort during the biopsy procedure (P less than 0.04) and had less memory for the procedure (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Biopsia con Aguja/métodos , Hepatopatías/diagnóstico , Midazolam/uso terapéutico , Adulto , Anciano , Humanos , Memoria/efectos de los fármacos , Midazolam/farmacología , Persona de Mediana Edad , Cooperación del Paciente , Encuestas y CuestionariosRESUMEN
This study compares the effects of two different benzodiazepines used for conscious sedation during combined upper gastrointestinal endoscopy (EGD) and colonoscopy. Subjects were assessed for their degree of analgesia and amnesia for the procedure, prior experience with endoscopy, and willingness to undergo another similar procedure should such be necessary. The patients were randomized single blind to receive either midazolam or diazepam for their preprocedure sedation. The amount of preprocedure sedation utilized was determined by titration of the dose to achieve slurring of speech. Prior to receiving either agent, the subjects were shown a standard card containing pictures of 10 common objects, were asked to name and remember them, and were told they would be "quizzed" (at 30 min and 24 hr) after being sedated for their recollection as to the objects pictured on the card. Each subject filled out a questionnaire addressing their perceived discomfort during the endoscopic procedure and their memory of the procedure 24 hr after the procedure. Sixty-three percent of the midazolam-sedated subjects reported total amnesia for their colonoscopy vs 20% of diazepam-sedated patients (P less than 0.001). Fifty-three percent of midazolam-sedated patients reported total amnesia of their upper gastrointestinal endoscopy vs only 23% of diazepam-sedated subjects (P less than 0.05). The midazolam-sedated subjects reported experiencing less pain with both upper gastrointestinal endoscopy (P less than 0.05) and colonoscopy (P less than 0.001) than did the diazepam-sedated group. Most importantly, the midazolam group was more willing to undergo another similar endoscopic procedure should they be asked to do so by their physician (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Diazepam/administración & dosificación , Sistema Digestivo , Endoscopía , Midazolam/administración & dosificación , Adulto , Anciano , Amnesia , Analgesia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distribución AleatoriaRESUMEN
Individuals undergoing hepatic and renal transplants are susceptible to infections of the gastrointestinal tract, particularly the esophagus. The most common responsible agents are Candida and herpes simplex virus (HSV) with cytomegalovirus (CMV), Aspergillus, and other agents being regarded as unusual pathogens even in this unique population. Altered T-cell populations have been associated with CMV colitis in healthy homosexuals and in individuals with the acquired immunodeficiency syndrome (AIDS). Similarly, individuals with Epstein-Barr virus infections have altered T-cell populations. Whether these infections alter T-cell populations in infected individuals or the abnormalities in T-cell subpopulations occur first and enhance the likelihood of an infection in susceptible populations is as yet unknown. In this study peripheral blood T-cell populations in individuals before (19 patients) and after (47 patients) liver transplantation and after receiving a renal allograft (21 patients) were compared. Those individual having any symptoms related to esophageal disease underwent upper gastrointestinal endoscopy combined with mucosal biopsies, brushings, and cultures and were subdivided into those with and without infectious esophagitis. CMV esophagitis was found to be associated with an arithmetically decreased T-cell helper/suppressor (H/S) ratio principally due to an increase in the suppressor cell number. Such a reduction in the TH/S ratio and in the number of circulating suppressor cells was not found in esophagitis due to either HSV or Candida and was unrelated to the serum cyclosporine level or prednisone dosage prescribed.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Candidiasis/inmunología , Infecciones por Citomegalovirus/inmunología , Esofagitis/etiología , Herpes Simple/inmunología , Trasplante de Riñón , Trasplante de Hígado , Linfocitos T/clasificación , Adulto , Ciclosporinas/uso terapéutico , Esofagitis/inmunología , Humanos , Persona de Mediana Edad , Prednisona/uso terapéuticoRESUMEN
Upper gastrointestinal endoscopy was performed for the evaluation of infectious esophagitis in 19 consecutive subjects evaluated prospectively before orthotopic liver transplantation (OLTx), in a separate group of 27 subjects post-OLTx, and in 21 subjects following orthotopic renal transplantation (ORTx). None of the pre-OLTx patients had evidence of infectious esophagitis, whereas 11% of the post-OLTx and 24% of the post-ORTx patients had esophageal infections. Candida esophagitis was found only in the post-ORTx patients, whereas cytomegalovirus and herpes simplex viral esophagitis were found in both the post-ORTx and post-OLTx patients. Dysphagia was associated with evidence of herpes simplex virus infection (P less than 0.001) and epigastric pain was associated with Candida infection (P less than 0.001). No association between the administration of prednisone or the blood level of cyclosporine A and esophagitis was found. Finally, the use of standard low-dose mycostatin prophylaxis was not effective for prevention of Candida esophagitis. Nonetheless the use of higher doses of mycostatin was therapeutic.