RESUMEN
We analysed liver histology findings in a large cohort of patients with chronic hepatitis C and in roughly half of them their response to interferon-alpha-based on iron parameters and HFE status. Histological activity and virological response to antiviral therapy (n = 146) were analysed in 273 immunocompetent and nonalcoholic patients with chronic hepatitis C, in terms of serum iron load, intrahepatic iron load (n = 110) and HFE mutations. Patients who were heterozygous for the C282Y and H63D mutations exhibited higher iron serum parameters than subjects without these mutations. The intrahepatic iron load was higher in H63D patients only. No association was observed between HFE mutations and histological activity. Increased iron parameters were associated with liver disease severity by univariate analysis only. Genotype 1 and ferritinaemia were associated with a poor response to antiviral therapy, whereas the H63D mutation emerged as a positive predictive factor for end of treatment and sustained antiviral response. Therefore, in chronic hepatitis C patients serum and intrahepatic iron levels were weakly correlated with histological activity, while HFE mutations were not. As for the response to interferon-alpha, elevated ferritinaemia constituted a negative predictive factor whereas the H63D mutation was a positive one. The H63D mutation might form part of an immunogenetic profile influencing the response to interferon therapy.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/genética , Antígenos de Histocompatibilidad Clase I/genética , Proteínas de la Membrana/genética , Polimorfismo Genético , Resultado del Tratamiento , Adolescente , Adulto , Sustitución de Aminoácidos/genética , Estudios de Cohortes , Femenino , Ferritinas/sangre , Proteína de la Hemocromatosis , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/patología , Heterocigoto , Humanos , Interferón-alfa/uso terapéutico , Hierro/análisis , Hierro/sangre , Sobrecarga de Hierro , Hígado/química , Hígado/patología , Masculino , Persona de Mediana Edad , Mutación/genética , Valor Predictivo de las Pruebas , ARN Viral/sangreRESUMEN
Air-filled paratracheal bronchogenic cysts are extremely rare. They are lined by respiratory epithelium. We have operated on 2 patients whose cysts were diagnosed by CT scan: one presenting with bloody sputum and the other with dysphagia. Both patients had a history of neck surgery. Because such cases are rare in the literature, their exact origin, whether tracheocele, diverticulum or other form of air-filled cyst, remains a matter of debate. However, their frequency is probably underestimated because most cause few symptoms and are well tolerated. In a recent radiologic study their prevalence was found to be 2% in patients undergoing CT scan.
Asunto(s)
Aire , Quiste Broncogénico/embriología , Enfermedades de la Tráquea/embriología , Biopsia , Quiste Broncogénico/complicaciones , Quiste Broncogénico/diagnóstico , Quiste Broncogénico/epidemiología , Quiste Broncogénico/cirugía , Trastornos de Deglución/etiología , Divertículo/embriología , Factores Epidemiológicos , Femenino , Hemoptisis/etiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Mucosa Respiratoria/embriología , Mucosa Respiratoria/patología , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: Gastrointestinal stromal tumors (GIST) are rare neoplasms, 1-3% of malignant gastrointestinal tumors. They are immature proliferations of spindled and/or epithelioid cells, developed in the muscular layer of the digestive tract, showing uncompleted or partial muscular, nervous or mixed differentiation. Immunohistologic knowledge about these tumors has recently progressed because of the discovery of specific markers (coexpression vimentin-CD117, oncogenes): GIST can now be distinguished from the other mesenchymal tumors. METHODS: Retrospective study of seven patients with GIST who received the same treatment. RESULTS: For our seven patients the mean age was 49 years with a male predominance (sex-ratio 4/3). The tumoral localisations are principally the small bowel (four cases), the rectum (two cases) and the stomach (one case). The treatment consisted of a first surgery, adapted to the tumoral localisation and extension, associated to chemotherapy in case of metastasis or local recurrence. The study of the histological grading for the seven patients showed tumors with poor prognoses. Six patients developed recurrence in a 2-year period; for the survey we are too close for a proper view. CONCLUSIONS: A review of the literature on stromal tumors finds older patients (59 years) with an equal sex ratio. Against the results of our series, the most frequent location is the stomach (50%). But the main problem is the better understanding of the particular evolution of these tumors. The bad short-date prognosis imposes carrying out larger studies, in order to confirm the principal hypothesis of histogenesis and to improve the survey by an optimal treatment.
Asunto(s)
Neoplasias Gastrointestinales/patología , Adulto , Anciano , Quimioterapia Adyuvante , Femenino , Neoplasias Gastrointestinales/inmunología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios Retrospectivos , Factores Sexuales , Razón de Masculinidad , Células del Estroma/patologíaRESUMEN
To analyze the spontaneous pathologic progression of chronic hepatitis C, we analyzed the histopathologic semiquantitative scores (Metavir and Knodell) of sequential liver biopsies performed in untreated hepatitis C virus (HCV)-infected patients. Subjects included 35 men and 41 women, with a mean age of 41 +/- 12 years, a duration of HCV infection of 11 +/- 5 years, and an interval between liver biopsies of 3.7 +/- 2.5 years. Results obtained using the Knodell score and the Metavir score were similar. At the first biopsy, 78.9% of patients had a low activity score (A0-A1) and 82.9% had a low fibrosis score (F0-F2). At the second biopsy, the activity decreased in 9.2%, was unchanged in 72.4%, and increased in 18.5%. An increase in activity was more frequently observed in patients infected with genotype 1 (28.9%) than with others (7.7%; P =.04); the yearly progression of activity was significantly higher in patients with a low rather than high initial activity score (0.11 v -0.02; P <.01). An increase in fibrosis was noted in 13.3% of those with a low and 43.8% of those with a high initial activity score (P <.01), with a highest rate of yearly fibrosis progression (0.12 U). In multivariate analysis, only a high activity score was significantly associated with an increased risk of fibrosis progression (relative risk, 25.5; 95% confidence interval, 2.7 to 238; P =.004). Spontaneous chronic hepatitis C evolution is worsening in only 20% of patients. Fibrosis progression is significantly associated with the necroinflammatory activity suggesting that this factor should be regarded as a major clue for deciding therapy.
Asunto(s)
Hepatitis C Crónica/diagnóstico , Hígado/patología , Adulto , Alanina Transaminasa/sangre , Anticuerpos Antivirales/análisis , Biopsia , Progresión de la Enfermedad , Femenino , Hepacivirus/clasificación , Hepacivirus/genética , Hepacivirus/inmunología , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/sangre , Humanos , Cirrosis Hepática/patología , Masculino , ARN Viral/análisisAsunto(s)
Infecciones por VIH/complicaciones , Hepatitis B/complicaciones , Biopsia , Didanosina/uso terapéutico , Quimioterapia Combinada , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Hepatitis B/diagnóstico , Hepatitis B/tratamiento farmacológico , Humanos , Lamivudine/uso terapéutico , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Saquinavir/uso terapéutico , Estavudina/uso terapéuticoRESUMEN
BACKGROUND: A prospective multicentre study was initiated in HCV-infected haemodialysis patients to assess the tolerance and efficacy of alpha-2b interferon. METHODS: We had planned to include 120 patients with HCV RNA detectable by polymerase chain reaction (PCR) (Amplicor Roche) and histologically documented chronic hepatitis. The dose of alpha-interferon was 3 million units (MU) three times weekly (TTW), to be reduced to 1.5 MU TTW in case of side-effects. Tolerance was evaluated monthly; virological efficacy was evaluated by PCR. A liver biopsy was performed at month 18 (M18). RESULTS: (a) TOLERANCE: After 37 patients had been included, the study was discontinued by the promoting institution because of severe side-effects requiring that treatment be stopped in 19 patients. The side-effects were: cardiac (4) neuropsychiatric (2), digestive (3), acute necrosis of the graft (1), severe asthenia (9), minor side-effects were observed in 22 patients. A complete 12-month course was completed in 12 patients for the 3 MU TTW dose and in six patients for the 1.5 MU TTW reduced dose. Normal ALT level (OR, 0.16; CI 95%, 0.03-0.89) at inclusion was associated with interruption of treatment (univariate analysis). (b) EFFICACY: Sustained virological response was observed in only seven (18.9%), of the 18 patients who completed the treatment (38%). Increased ALT at inclusion (OR, 1.04; CI 95%, 1.01-1.09) and cumulated doses of interferon (OR, 1.01; CI 95%, 1.004-1.026) were jointly associated with a sustained response, while positive PCR at M2 was strongly predictive of treatment failure. CONCLUSION: Tolerance of interferon is poor in haemodialysis patients. Sustained response is fairly high in patients who have 12 months of treatment and seems to be based on the immune status of the patients (ALT) and the cumulative doses of interferon.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Diálisis Renal , Adulto , Antivirales/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Hepatitis C/sangre , Hepatitis C/enzimología , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes , Resultado del TratamientoRESUMEN
The authors report the third case of primary adenocarcinoma of the rectovaginal septum without associated endometriosis and discuss the pathogenesis of this tumour. Some of the tumour cells were stained with OC 125 antibody which recognises epithelium of coelomic origin; adenocarcinoma of the rectovaginal septum may arise directly from embryological Müllerian remnants.
Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/terapia , Neoplasias Vaginales/diagnóstico , Neoplasias Vaginales/terapia , Adenocarcinoma/patología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias del Recto/patología , Neoplasias Vaginales/patologíaRESUMEN
There is evidence of deterioration of hepatitis C after pregnancy. To investigate potential histological changes, we compared liver biopsy samples taken before and after delivery from 12 women positive for hepatitis C virus (HCV) and 12 nonpregnant HCV-positive women. Semiquantitative histopathological measurements showed greater deterioration in cases than in controls (necroinflammatory score deterioration 83.3% vs 25.0%; fibrosis score 41.6% vs 8.3%). This case-control study suggests that pregnancy may worsen HCV-related histopathological injury.
Asunto(s)
Hepatitis C Crónica/patología , Complicaciones Infecciosas del Embarazo/patología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Hígado/enzimología , Hígado/patología , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Transaminasas/metabolismoRESUMEN
The objective of the study was to quantify the kinetics of the superparamagnetic nanoparticle ferumoxtran (AMI 227, Sinerem(R), Combidex(R)) in the efferent lymph of the subdiaphragmatic lymph nodes and in various node groups of the rat to elucidate the uptake mechanism. The thoracic lymph duct was catheterized in 24 rats after an IV injection of 40 micromol Fe/kg ferumoxtran. Three rats were studied at several time points between 1.5 and 24 hours. At each time point, 0.3 ml of lymph were collected over 45 minutes. Lymph nodes were differentiated into five groups. The iron concentration in the samples and in plasma was measured by relaxometry at 0.47 T and atomic absorption spectrometry. Cytology was performed on the lymph. High concentrations of nanoparticles were found in the thoracic lymph soon after injection (90 minutes). No particle was found in the lymph cells, indicating that ferumoxtran was extracellular in the lymph fluid. The maximum concentration was reached later in all node groups, at 12 hours, and then plateaued. The transcapillary pathway and subsequent lymph drainage of the particles seem to play a major role in the delivery to the lymph nodes.
Asunto(s)
Medios de Contraste/administración & dosificación , Medios de Contraste/farmacocinética , Hierro/administración & dosificación , Hierro/farmacocinética , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/metabolismo , Imagen por Resonancia Magnética/métodos , Óxidos/administración & dosificación , Óxidos/farmacocinética , Animales , Dextranos , Femenino , Óxido Ferrosoférrico , Inyecciones Intravenosas , Ganglios Linfáticos/efectos de los fármacos , Linfografía/métodos , Nanopartículas de Magnetita , Modelos Animales , Probabilidad , Ratas , Ratas Endogámicas F344 , Sensibilidad y EspecificidadRESUMEN
Narcotic substitution is now widely used. Morphine can induce a spasm of the sphincter of Oddi but dilation of bile duct has been reported only in an anecdotal case. In June 1995, we observed a first case of dilation of the common bile duct without organic obstacle in a hepatitis C virus (HCV)-infected patient who was under narcotic substitution, suggesting a causal relationship. We conducted a prospective study to evaluate the precise prevalence of bile duct abnormalities related to narcotic substitution in active intravenous drug or ex-intravenous drug users referred to our liver unit for histologic evaluation of HCV infection. We conducted a prospective study in a 30-month period of 334 HCV-infected patients, including 36 receiving narcotic substitution with methadone or buprenorphine. Biliary tract was analyzed by ultrasonography and by endoscopy ultrasound in cases of bile duct abnormalities. Of the 36 patients under narcotic substitution, 3 (8.3%) had asymptomatic dilated bile duct without organic obstacle--defined as a common bile duct > or =9 mm--compared to 1 of 298 (0.03%; p < 0.001) of those who did not receive substitution. Narcotic substitution may lead to bile duct dilation that does not require invasive diagnosis procedures.
Asunto(s)
Enfermedades de los Conductos Biliares/inducido químicamente , Buprenorfina/efectos adversos , Metadona/efectos adversos , Narcóticos/efectos adversos , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/rehabilitación , Adulto , Enfermedades de los Conductos Biliares/diagnóstico por imagen , Enfermedades de los Conductos Biliares/patología , Conductos Biliares/patología , Biopsia , Conducto Colédoco/patología , Enfermedades del Conducto Colédoco/inducido químicamente , Enfermedades del Conducto Colédoco/diagnóstico por imagen , Enfermedades del Conducto Colédoco/patología , Dilatación Patológica , Endoscopía , Femenino , Seronegatividad para VIH , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/patología , Humanos , Hígado/patología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Estudios Prospectivos , UltrasonografíaRESUMEN
A perfect metabolic correction of diabetes is essential to completely eradicate long-term chronic complications. Only a total pancreatic graft with portal venous drainage enables such an achievement. Isogenic Lewis rats were used for donors, recipients and controls. Pancreatico-duodenal transplantation was either heterotopic with systemic venous drainage (n = 12) or paratopic with portal drainage (n = 11). All animals were regularly monitored for non-fasting plasma glucose and insulin. Both techniques promptly restored the non-fasting plasma glucose to normal values (p<0.003). Normo-insulinemia (47.4+/-6.4 microU/ml) was obtained in the paratopic group, while the heterotopic group showed hyperinsulinism (132.0+/-15.2 microU/ml). Perfect metabolic control justifies the additional technical difficulties of total paratopic pancreatic transplantation with portal venous drainage.
Asunto(s)
Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/cirugía , Duodeno/trasplante , Trasplante de Páncreas , Páncreas/irrigación sanguínea , Vena Porta/fisiopatología , Animales , Glucemia/análisis , Diabetes Mellitus Experimental/fisiopatología , Duodeno/irrigación sanguínea , Femenino , Insulina/sangre , Periodo Posoperatorio , Ratas , Ratas Endogámicas Lew , Trasplante HeterotópicoRESUMEN
Hereditary nonpolyposis colorectal cancer (HNPCC) is an inherited predisposition to colorectal and endometrial cancers caused by germline mutation of mismatch repair genes, with hMLH1 and hMSH2 underlying the majority of the cases. Although lymphoid tumors are the most common tumors in mouse models for HNPCC, lymphomas are almost never encountered in patients who have HNPCC, except in rare families with germline homozygous deletion of hMLH1. We report the case of a 53-year-old man who had a history of colon cancers related to constitutional hMLH1 mutation and who was diagnosed as having a duodenal follicular lymphoma This diagnosis was supported by IgH-BCL2 rearrangement and BCL2 immunoreactivity in tumor cells. The association of both of these possibly related rare diseases has never been reported. To clarify this relationship, we searched for hMLH1 expression and mismatch repair deficiency in the duodenal lymphoma. hMLH1 immunostaining was positive in lymphoid tumor cells, and no microsatellite instability was detected. In agreement with mouse models for HNPCC, these results suggest the involvement of alternative mechanisms to complete mismatch repair deficiency for lymphomagenesis in HNPCC syndrome.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Proteínas de Unión al ADN , Neoplasias Duodenales/patología , Linfoma Folicular/patología , Proteínas Adaptadoras Transductoras de Señales , Antígenos CD20/análisis , Complejo CD3/análisis , Proteínas Portadoras , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , ADN de Neoplasias/genética , Neoplasias Duodenales/genética , Neoplasias Duodenales/metabolismo , Reordenamiento Génico , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunohistoquímica , Linfoma Folicular/genética , Linfoma Folicular/metabolismo , Masculino , Persona de Mediana Edad , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS , Mutación , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/genética , Neprilisina/análisis , Proteínas Nucleares , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-2/genéticaRESUMEN
PURPOSE: The tumor suppressor gene p53 plays a crucial role in cell cycle control and apoptosis in response to DNA damages. p53 gene mutations and allelic losses at 17p are one of the most common genetic alterations in primary head and neck squamous cell carcinoma (HNSCC). Alterations of the p53 gene have been shown to contribute to carcinogenesis and drug resistance. PATIENTS AND METHODS: In this prospective series, patients with HNSCC were treated with cisplatin-fluorouracil neoadjuvant chemotherapy. p53 status was characterized in 106 patients with HNSCC (p53 mutations, allelic losses at p53 locus, and plasma anti-p53 antibodies) to determine the existence of a relationship between p53 gene status and response to neoadjuvant chemotherapy. RESULTS: Exons 4 to 9 of the p53 gene were analyzed, and mutations were found in 72 of 106 patients with HNSCC. p53 mutations were associated with loss of heterozygosity at chromosome 17p (P <.001). The prevalence of p53-mutated tumors was higher in the group of patients with nonresponse to neoadjuvant chemotherapy than in the group of responders (81% v 61%, respectively; P <.04). When compiling p53 mutations and anti-p53 antibodies in plasma, the correlation between p53 status and response to chemotherapy was significant (87% v 57%, respectively; P =.003). A multivariate analysis showed that p53 status is an independent predictive factor of response to chemotherapy. CONCLUSION: This prospective study suggests that p53 status may be a useful indicator of response to neoadjuvant chemotherapy in HNSCC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Genes p53/genética , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Adulto , Carcinoma de Células Escamosas/patología , Ciclofosfamida/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Neoplasias de Cabeza y Cuello/patología , Humanos , Pérdida de Heterocigocidad , Masculino , Terapia Neoadyuvante , Valor Predictivo de las Pruebas , Estudios Prospectivos , Resultado del TratamientoRESUMEN
The VIPoma syndrome is rare. It is usually caused by a neuroendocrine tumor located in the pancreas. Somatostatin analogs and interferon-a can be helpful in the symptomatic control of the disease, but the efficacy of chemotherapy in metastatic disease is limited. We report the case of a 32-yr-old patient who had a primary intestinal VIPoma with peritoneal carcinomatosis and hepatic metastases. Somatostatin analogs and conventional chemotherapy regimens were not effective on VIPoma syndrome and tumor progression. The combination of 5- fluorouracil and interferon-alpha was associated with a major clinical improvement and tumor regression. Further investigations should evaluate the place of such a combination as a first line treatment for patients with metastatic neuroendocrine tumors.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Yeyuno/patología , Vipoma/tratamiento farmacológico , Vipoma/secundario , Adulto , Fluorouracilo/administración & dosificación , Humanos , Interferón-alfa/administración & dosificación , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Tomografía Computarizada por Rayos X , Vipoma/diagnóstico por imagenAsunto(s)
Trasplante de Corazón , Neoplasias Pulmonares/epidemiología , Adulto , Anciano , Femenino , Trasplante de Corazón/mortalidad , Trasplante de Corazón/fisiología , Humanos , Incidencia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE: Malignant mediastinal lymph nodes with unknown primary tumor is a rare occurrence. The purpose of this study is to specify some characteristics of the patients presenting with this disease and to define an adequate therapeutic approach. MATERIAL AND METHODS: Between 1985 and 1997, we have operated on 54 patients with isolated non-small cell malignancy to mediastinal lymph nodes. Forty-nine patients underwent surgical biopsy of the mediastinal mass, generally followed by radiation therapy and/or chemotherapy. A mediastinal lymph node resection was performed in 5 patients. RESULTS: Five patients were lost to follow-up (9.3%). The 5-year survival rate and the median survival were 12.4 +/- 5% and 7 months respectively. Four of the 7 patients who were still alive after follow-ups ranging from 10 to 68 months had undergone a lymph node resection. During the follow-up, a primary tumor was discovered in only 5 patients (11.4%). CONCLUSIONS: Patients with isolated malignant lymph nodes of the mediastinum have a poor prognosis. In order to improve their survival, we recommend a more aggressive therapeutic approach comprising a chemotherapy and a mediastinal lymph node resection, associated in some cases with a lung resection. Radiation therapy of the mediastinum can be administered, principally in case of incomplete resection.
Asunto(s)
Carcinoma de Células Pequeñas/secundario , Metástasis Linfática/patología , Neoplasias del Mediastino/secundario , Neoplasias Primarias Desconocidas/patología , Análisis Actuarial , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Biopsia , Carcinoma de Células Pequeñas/mortalidad , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Pequeñas/terapia , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Masculino , Neoplasias del Mediastino/mortalidad , Neoplasias del Mediastino/patología , Neoplasias del Mediastino/terapia , Persona de Mediana Edad , Neumonectomía , Pronóstico , Radioterapia Adyuvante , Análisis de SupervivenciaRESUMEN
Hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) gene was identified because of its increased expression in 25% of human hepatocellular carcinoma. HIP/PAP protein, a C-type lectin, binds laminin, acts as an adhesion molecule for hepatocytes, and has also been described as an acute phase secretory protein during acute pancreatitis in humans and rats. We investigated HIP/PAP protein expression in patients with various liver diseases associated with ductular reaction. At the same time, we analyzed patients with hepatocellular carcinoma and cholangiocarcinoma, and tested HIP/PAP protein levels in sera to establish the pattern of secretion. Our data show that HIP/PAP expression was not restricted to hepatocellular carcinoma, but was also detected in cholangiocarcinoma cells as well as in reactive non-malignant bile ductules. In contrast, HIP/PAP protein expression was undetectable in normal mature hepatocytes, but some ductular cells localized at the interface of portal tracts with parenchyma were HIP/PAP immunoreactive in normal liver. Finally, we present evidence that HIP/PAP serum levels were increased in 21/28 (75%) patients with hepatocellular carcinoma, and in 25/51 (49%) patients with nonmalignant cirrhosis. Altogether, these results suggest that HIP/PAP protein may be implicated in hepatocytic and cholangiolar differentiation and proliferation.
Asunto(s)
Proteínas de Fase Aguda/biosíntesis , Antígenos de Neoplasias , Neoplasias de los Conductos Biliares/metabolismo , Conductos Biliares Intrahepáticos/metabolismo , Biomarcadores de Tumor , Carcinoma Hepatocelular/metabolismo , Colangiocarcinoma/metabolismo , Lectinas Tipo C , Neoplasias Hepáticas/metabolismo , Adulto , Anciano , Animales , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Carcinoma Hepatocelular/patología , Colangiocarcinoma/patología , Femenino , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Proteínas Asociadas a Pancreatitis , RatasRESUMEN
Molecular studies have revealed that microsatellite instability and loss of heterozygosity occurred in head-and-neck cancer, suggesting the involvement both of suppressor and of mutator pathways in head-and-neck carcinogenesis. There is evidence for relations between tumor phenotype and clinical parameters. Indeed, replication-error phenotype, characterized by microsatellite instability, was associated with decreased sensitivity to chemotherapeutic agents in cell lines. Loss of heterozygosity is a frequent mechanism of inactivation of tumor-suppressor genes, which might be implicated in resistance to chemotherapy. In head-and-neck cancer, chemosensitivity is inconstant, and no marker is available to predict response to treatment. In order to evaluate the role of tumor phenotype on resistance to chemotherapy, we analyzed 56 primary head-and-neck squamous-cell carcinomas collected at time of diagnosis and a sub-group of 23 resistant tumors collected after chemotherapy at 22 microsatellite loci. At time of diagnosis, only one tumor showed MSI-H phenotype. Loss of heterozygosity (LOH) was observed in 75% of tumors, indicating the dominant role of the suppressor in comparison with the mutator pathway in HNSCC carcinogenesis. No change in microsatellite patterns was observed after treatment, suggesting that chemotherapy did not select mismatch-repair-deficient clones. Univariate analyses showed that LOH at 9p or 17p was significantly associated with drug resistance. In a multivariate analysis, only LOH at 17p remains predictive of low response to chemotherapy, with a relative risk of 3.7 and 95% CI of 1.1-13, indicating that p53 alterations could play a role in chemotherapy resistance in HNSCC. Int. J. Cancer (Pred. Oncol.) 84:410-415, 1999.