Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Piomiositis/tratamiento farmacológico , Piomiositis/microbiología , Absceso/tratamiento farmacológico , Absceso/microbiología , Adulto , Anciano , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients with metastatic pancreatic adenocarcinoma were randomized in a 2:1 fashion to gemcitabine 1000 mg/m(2) weekly for 3 weeks of a 4-week cycle plus rigosertib 1800 mg/m(2) via 2-h continuous IV infusions given twice weekly for 3 weeks of a 4-week cycle (RIG + GEM) versus gemcitabine 1000 mg/m(2) weekly for 3 weeks in a 4-week cycle (GEM). RESULTS: A total of 160 patients were enrolled globally and randomly assigned to RIG + GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG + GEM group versus 6% in the GEM group), hyponatremia (17% versus 4%), and anemia (8% versus 4%). The median overall survival was 6.1 months for RIG + GEM versus 6.4 months for GEM [hazard ratio (HR), 1.24; 95% confidence interval (CI) 0.85-1.81]. The median progression-free survival was 3.4 months for both groups (HR = 0.96; 95% CI 0.68-1.36). The partial response rate was 19% versus 13% for RIG + GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40 cases). Other mutations detected included TP53 (13 cases) and PIK3CA (1 case). No correlation between mutational status and efficacy was detected. CONCLUSIONS: The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Glicina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Sulfonas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Proteínas de Ciclo Celular/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasa Clase I , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Glicina/efectos adversos , Glicina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/genética , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas p21(ras)/genética , Sulfonas/efectos adversos , Proteína p53 Supresora de Tumor/genética , Gemcitabina , Quinasa Tipo Polo 1 , Neoplasias PancreáticasRESUMEN
Most frequently the use of bioactive molecules for the supplementation of food and beverages is hampered by stability limitations or inadequate intestinal absorption. This work evaluates in vitro the role that the interface of the nanoemulsion has on the physicochemical properties, the stability behavior and the enzymatic degradation after oral intake. For that purpose three soybean oil (SB) formulations were studied. These formulations were based on the emulsifier lecithin but modified with two non-ionic surfactants Pluronic(®) F68 (PF68) or Pluronic(®) F127 (PF127) yielding (i) SB-NE (only lecithin on the interface), (ii) SB-NE PF68 (lecithin plus PF68) and 9 (iii) SB-NE PF127 (lecithin plus PF127). All the formulations tested were low polydispersed and showed a size of about 200 nm and ζ-potential of -50 mV. The in vitro colloidal stability assay showed that lecithin itself was able to promote that formulations reach unaltered to the small intestine and facilitate the absorption of the antioxidant payload on a tunable fashion there (with in vitro bioaccessibility values from around 40% up to a 70%). PF68 was able to sterically stabilize the formulation against the aggregation induced by the pH and electrolytes of the simulated gastrointestinal track; however, this surfactant was easily displaced by the lipases of the simulated intestinal milieu being unable to modulate the digestion pattern of the oil droplets in the small intestine. Finally, PF127 displayed a strong steric potential that dramatically reduced the interaction of the oil droplets with lipases in vitro, which will compromise the capacity of the formulation to improve the bioaccessibility of the loaded antioxidant.
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Antioxidantes/química , Emulsiones/química , Nanopartículas/química , Fármacos Neuroprotectores/química , Disponibilidad Biológica , Química Farmacéutica/métodos , Portadores de Fármacos/química , Emulsionantes/química , Lecitinas/química , Tamaño de la Partícula , Aceite de Soja/químicaRESUMEN
BACKGROUND: Trastuzumab has been approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric carcinoma; however, relatively little is known about the role of HER2 in the natural history of this disease. PATIENTS AND METHODS: Patients enrolled in the INT-0116/SWOG9008 phase III gastric cancer clinical trial with available tissue specimens were retrospectively evaluated for HER2 gene amplification by FISH and overexpression by immunohistochemistry (IHC). The original trial was designed to evaluate the benefit of postoperative chemoradiation compared with surgery alone. RESULTS: HER2 gene amplification rate by FISH was 10.9% among 258 patients evaluated. HER2 overexpression rate by IHC was 12.2% among 148 patients evaluated, with 90% agreement between FISH and IHC. There was a significant interaction between HER2 amplification and treatment with respect to both disease-free survival (DFS) (P = 0.020) and overall survival (OS) (P = 0.034). Among patients with HER2-non-amplified cancers, treated patients had a median OS of 44 months compared with 24 months in the surgery-only arm (P = 0.003). Among patients with HER2-amplified cancers, there was no significant difference in survival based on treatment arm. HER2 status was not a prognostic marker among patients who received no postoperative chemoradiation. CONCLUSION: Patients lacking HER2 amplification benefited from treatment as indicated by both DFS and OS. CLINICAL TRIAL: INT-0116/SWOG9008 phase III.
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Adenocarcinoma/genética , Neoplasias Esofágicas/genética , Unión Esofagogástrica/patología , Amplificación de Genes , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Quimioradioterapia Adyuvante , Ensayos Clínicos Fase III como Asunto , Supervivencia sin Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/terapia , Femenino , Fluorouracilo/uso terapéutico , Gastrectomía , Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Chemotherapy represents the standard treatment for patients with metastatic stomach cancer. Conflicting results have been published regarding the activity of paclitaxel in this setting. Therefore, we developed a phase II study to evaluate an outpatient 3 h infusion of paclitaxel. METHODS: Patients with chemonaive metastatic stomach cancer received paclitaxel 210 mg/m(2) every 3 weeks. Patients with esophageal cancer were not eligible. RESULTS: Twenty-one patients were enrolled. The median age was 55.5 years (range 37-81 years). Two partial responses were observed among the 18 patients evaluable for response and toxicity (response rate 11%, 95% CI: 2-33%). The median time to progression was 10.5 weeks and median survival 23 weeks. There was only one episode of grade IV neutropenia and no episodes of grade 3-4 non-hematological toxicity were observed. CONCLUSION: Paclitaxel exhibited minimal activity in this patient population.
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Adenocarcinoma/tratamiento farmacológico , Atención Ambulatoria , Antineoplásicos Fitogénicos/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/efectos adversos , Esquema de Medicación , Femenino , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Paclitaxel/efectos adversos , Neoplasias Gástricas/patologíaRESUMEN
To enhance the specificity and sensitivity of serological detection of swine exposed to Ornithodoros erraticus or O. moubata, we purified the 158, 186, 215 and 260 kDa antigens from the former species and the designated (owing to their MW and charge) 19C, 17A, 20A1 and 20A2 antigens of the latter by HPLC and gel electroelution methods. All the O. erraticus antigens share epitopes and are difficult to purify individually by reverse phase and ion-exchange chromatography due to their molecular similarity. Tested individually by ELISA, all of them give the same optical densities (OD) with anti-O. erraticus sera, and these ODs are always lower with anti-immature than with anti-adult sera. Although immature and adult specimens have the same antigens, immature forms induce more anti-carbohydrate antibodies than adults. This is the reason for the lower ODs of the anti-immature sera against purified antigens, since these latter antigens essentially react with anti-peptide antibodies (hence, increasing the specificity and sensitivity of the serology). The N-terminus of the 260 kDa antigen shows 80-90% similarity with the hemoglobin alpha-chain of many mammals. The antigens of O. moubata are proteins that are very different from one another and are, therefore, readily purified by ion exchange chromatography. The 20A1 antigen appears to be the most immunogenic and is recognized equally by anti-immature and anti-adult sera. This antigen does not give false positive reactions with the negative control sera analyzed and its N-terminus region shares 46.2% homology with the alpha-chain of the C3 component of rabbit complement.
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Antígenos/aislamiento & purificación , Enfermedades de los Porcinos/diagnóstico , Infestaciones por Garrapatas/veterinaria , Garrapatas/inmunología , Secuencia de Aminoácidos , Animales , Anticuerpos/sangre , Antígenos/química , Cromatografía Líquida de Alta Presión/veterinaria , Cromatografía por Intercambio Iónico/veterinaria , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Masculino , Datos de Secuencia Molecular , Conejos , Sensibilidad y Especificidad , Análisis de Secuencia de Proteína , Homología de Secuencia de Aminoácido , Porcinos , Infestaciones por Garrapatas/diagnóstico , Garrapatas/químicaRESUMEN
We report a case of ticlopidine-induced prolonged cholestasis in a 60-year-old man with no previous hepatobiliary disease who presented with sudden right upper abdominal pain, jaundice and pruritus three months after starting ticlopidine therapy. Other drugs taken by the patient were not considered probable causes. The diagnostic evaluation showed no biliary obstruction and other possible causes of intra-hepatic cholestasis were excluded. The liver biopsy showed a cholestatic hepatitis with bile duct damage. The disease ran a severe and protracted course, but symptoms and jaundice eventually subsided five months after drug withdrawal. More than a year later, relevant abnormalities of liver function tests consistent with anicteric cholestasis still persist, fulfilling criteria for a minor form of drug-induced prolonged cholestasis. This syndrome has been reported infrequently in relation to several drugs, mainly chlorpromazine, and only once with ticlopidine.
Asunto(s)
Colestasis/inducido químicamente , Inhibidores de Agregación Plaquetaria/efectos adversos , Ticlopidina/efectos adversos , Colestasis/fisiopatología , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
This is the report of an unusual foreign body in the rectum which was a complication of the migration of an esophageal Celestin's prosthesis.
Asunto(s)
Trastornos de Deglución/terapia , Esófago , Migración de Cuerpo Extraño , Recto , Stents , Anciano , Anciano de 80 o más Años , Humanos , MasculinoRESUMEN
PURPOSE: We have previously shown that relative thymidylate synthase (TS) mRNA levels in primary gastric adenocarcinomas treated with fluorouracil (5-FU) and cisplatin are inversely associated with response and survival. This is a presumed function of TS as a target for 5-FU activity. We now test the hypotheses that the relative mRNA level of the excision repair cross-complementing (ERCC1) gene is inversely associated with response and survival as an independent function of cisplatin efficacy. PATIENTS AND METHODS: Patients had intact, untreated, primary gastric adenocarcinoma cancer and were evaluated for eligibility on a preoperative cisplatin infusion-5-FU protocol. cDNA, derived from primary gastric tumors before chemotherapy, was used to determine ERCC1 mRNA levels, expressed as the ratio of polymerase chain reaction (PCR) product of the ERCC1 gene and the beta-actin gene. RESULTS: The median ERCC1 mRNA level from 38 primary gastric cancers (33 assessable for response) was 5.8 x 10(-3) (range, 1.8 x 10(-3) to 19.5 x 10(-3)). Of 17 responding patients, 13 (76%) were less than or equal to 5.8 x 10(-3) and four were greater than 5.8 x 10(-3) (P = .003). The median survival for patients with ERCC1 mRNA levels less than or equal to 5.8 x 10(-3) has not been reached, whereas for those greater than 5.8 x 10(-3) it was 5.4 months (P = .034). The median TS mRNA level, 3.7 x 10(-3) (range, 0.9 to 18.9) also segregated responsive versus resistant tumors (P = .024). With both ERCC1 and TS mRNA levels below their medians, 11 of 13 patients (85%) responded; with both ERCC1 and TS mRNA levels above their medians, two of 10 patients (20%) responded (P = .003). CONCLUSION: Considered separately, either ERCC1 or TS mRNA levels in a primary gastric adenocarcinoma has a statistically significant relationship to response. ERCC1 mRNA levels have a statistically significant association with survival; in this cohort TS mRNA levels did not reach statistically significant association with survival as in our previous publication. Whether these molecular parameters are independent of each other as predictors of outcome remains to be determined.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Proteínas de Unión al ADN , Endonucleasas , Proteínas/análisis , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Timidilato Sintasa/análisis , Adenocarcinoma/química , Adenocarcinoma/cirugía , Cisplatino/administración & dosificación , Terapia Combinada , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Estudios Prospectivos , Proteínas/genética , ARN Mensajero/análisis , Neoplasias Gástricas/química , Neoplasias Gástricas/cirugía , Timidilato Sintasa/genéticaRESUMEN
We analysed in mice why the salivary gland extract (SGE-2) from Ornithodoros erraticus and O. moubata induce a protective response with Freund's adjuvants (FAs) in swine while the saliva, in natural conditions, does not. Such protection has been ascribed to the fact that administration of SGE-2 plus FAs permits the recognition of certain salivary components that under natural conditions are not immunogenic. The present findings confirm this hypothesis since in mice, which are unable to recognize the above components, the SGE-2-FAs do not induce any protection. We rule out the possibility that the cause of this could lie in the absence of prostaglandin E2 in the SGE-2 (vs saliva) since it is not present in either fluid. Neither could it be due to a change in antibody isotype since those induced by parasites bites and by the SGE-2-FAs are the same (IgG2a > IgG1 > IgG2b; not IgG3, IgM, IgE). No IgG2a were seen when the SGE-2 were administered alone or with alum or ricin. It is therefore suggested that first responses would be Th1 and the second ones Th2, although no IgE is seen in the latter responses either. The parasites do not require complement to feed; by contrast, they block its activation and skin cellular infiltrates, such as those elicited by IL-8, MCP-1 and C5a, do not affect them, regardless of the presence or not of antitick antibodies.
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Garrapatas/inmunología , Compuestos de Alumbre/farmacología , Animales , Anticuerpos/inmunología , Antígenos/inmunología , Western Blotting , Proteínas del Sistema Complemento/inmunología , Dinoprostona/análisis , Conducta Alimentaria , Adyuvante de Freund/farmacología , Isotipos de Inmunoglobulinas/clasificación , Isotipos de Inmunoglobulinas/inmunología , Ratones , Ricina/farmacología , Saliva/química , Porcinos , Garrapatas/metabolismo , Vacunas/inmunologíaRESUMEN
We show by sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blot that the composition of the soluble extracts of salivary glands (SGE-2) of Ornithodoros erraticus and Ornithodoros moubata is similar to that of the saliva (pilocarpine-induced), and that the extracts are a valid source of antigens for the detection of anti-argasid antibodies. It is also shown that the SGE-2s do not vary qualitatively with the developmental stage, physiological status, or sex of the ticks. The antigenic components (at least in O. erraticus) are released into the SGE-2 by the action of enzymes that can be inhibited by phenylmethane sulfonyl fluoride plus EDTA. Most of the components of the SGE-2, except the antigenic ones, are strongly glycosylated. Accordingly, the deglycosylation of the SGE-2s does not affect the recognition of antigenic components by anti-tick sera. In both species, the major components of the SGE-2s or the saliva are not recognized by the corresponding antisera. These nonimmunogenic components could have vaccinal value but not diagnostic interest. Finally, it is shown that the antigens of O. erraticus and O. moubata do not cross-react with one another and that those of the first species are more antigenic than those of the second.
Asunto(s)
Antígenos , Enfermedades de los Porcinos/diagnóstico , Infestaciones por Garrapatas/veterinaria , Garrapatas/inmunología , Animales , Antígenos/química , Antígenos/inmunología , Western Blotting/veterinaria , Reacciones Cruzadas , Electroforesis en Gel de Poliacrilamida/veterinaria , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Sueros Inmunes/inmunología , Masculino , Peso Molecular , Saliva/inmunología , Glándulas Salivales/inmunología , Factores Sexuales , Porcinos , Enfermedades de los Porcinos/inmunología , Infestaciones por Garrapatas/diagnóstico , Infestaciones por Garrapatas/inmunologíaRESUMEN
PURPOSE: Response rates to fluorouracil (5-FU)-based therapy remain low. As new, active agents are being tested, information regarding specific intratumoral genetic determinants of chemotherapy sensitivity or resistance can be used to plan therapy rationally. Intratumoral thymidylate synthase (TS) quantitation may be among the most important determinants of sensitivity or resistance to 5-FU. MATERIALS AND METHODS: Forty-six disseminated colorectal cancer patients had measurable tumor biopsies for polymerase chain reaction (PCR)-based determination of TS mRNA pretreatment. Protracted infusion of 5-FU 200 mg/m2/d for 21 days with weekly intravenous leucovorin 20 mg/m2 each cycle was given. After two cycles, responses were evaluated. Response data were correlated with independently determined intratumoral ratios of TS/beta-actin mRNA for each patient. RESULTS: TS/beta-actin ratios were successfully obtained for 42 patients (91%). TS/beta-actin ratios ranged from 0.3 x 10(-3) to 18.2 x 10(-3) (median, 3.5 x 10[-3]). Twelve patients (26%) responded to treatment (median TS/beta-actin ratio, 1.7 x 10[+3]). Thirty-four patients did not respond (median TS/beta-actin ratio, 5.6 x 10[-3]). No patient with a TS mRNA level greater than 4.1 x 10(-3) responded. The median TS/beta-actin ratio (3.5 x 10[-3]) significantly segregated responders from nonresponders (P = .001). Median survival for patients with TS/beta-actin ratios < or = 3.5 x 10(-3) was 13.6 months; for patients with TS/beta-actin ratios greater than 3.5 x 10(-3), it was 8.2 months (P = .02). CONCLUSION: For this cohort, the intratumoral TS/beta-actin ratio had a statistically significant association with response and survival. This relationship for other 5-FU schedules remains unknown. Confirmation of these data in a larger patient population could lead to determination of therapy for disseminated colorectal cancer based on a specific intratumoral molecular parameter.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Leucovorina/administración & dosificación , Timidilato Sintasa/análisis , Actinas/análisis , Anciano , Antídotos/administración & dosificación , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Esquema de Medicación , Resistencia a Antineoplásicos , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Because only approximately 50% of gastric carcinomas are resectable for cure, the authors hypothesized that effective systemic preoperative (neoadjuvant) chemotherapy, aimed at decreasing the size and extent of the primary tumor and eradicating distant microscopic disease, may increase the rate of resectability and have a greater impact on survival than postoperative (adjuvant) treatment alone. In addition, because the peritoneal cavity is the most common site of first recurrence after successful gastric cancer resection, intraperitoneal (IP) chemotherapy seemed a logical choice for postoperative (adjuvant) treatment. METHODS: Fifty-nine patients with invasive primary gastric adenocarcinoma who were deemed resectable for cure entered a clinical trial that called for 2 cycles of protracted infusion 5-fluorouracil with weekly leucovorin and cisplatin chemotherapy followed by surgery. Approximately 3-4 weeks after potentially curative surgery, patients were scheduled to receive two cycles of IP 5-fluoro-2'deoxyuridine and cisplatin. RESULTS: Of the 59 patients studied, 58 (98%) received both cycles of systemic chemotherapy. Fifty-six patients (95%) underwent surgery: 40 patients (71%) had resections intended to cure for Stage 0-IIIB disease, 15 patients (27%) had palliative surgery for Stage IV gastric carcinoma, and one patient died intraoperatively without being staged. Two patients refused surgery, and the remaining patient died of progressive disease prior to surgery. Thirty-one of the 40 patients who underwent curative surgery completed both cycles of postoperative IP therapy; 4 patients received only 1 cycle. Three patients (5%) died secondary to treatment complications. There were two operative deaths, and one patient died of peritonitis associated with Grade 4 granulocytopenia. Nine of the 40 patients (23%) whose carcinomas were resected for cure had recurrent carcinoma. With a median follow-up period now exceeding 45 months, the calculated median survival for the 59 patients entered into the trial is >4 years. CONCLUSIONS: This program of preoperative systemic and postoperative IP chemotherapy has been found to be safe and appears to decrease gastric carcinoma recurrence rates and increase survival compared with historic controls.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Esquema de Medicación , Femenino , Floxuridina/administración & dosificación , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intravenosas , Infusiones Parenterales , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Tomografía Computarizada por Rayos XRESUMEN
We report a case of portal hypertension associated with a non-traumatic arteriovenous fistula, presenting with bleeding duodenal varices. The patient was admitted for melaena. Emergency endoscopy showed oesophageal varices with no signs of recent bleeding and with no blood in the upper gastrointestinal tract. Arteriography of the coeliac axis and superior mesenteric artery failed to detect any bleeding source. Endoscopy was repeated because of persistent bleeding and revealed active bleeding from varices in the distal duodenum. The patient underwent surgery and a large paraduodenal varicose vein associated with an arteriovenous fistula was found. Resection of the paramural varix and surgical occlusion of the arteriovenous fistula were effective in the control of bleeding. Liver biopsy revealed mild portal fibrosis without cirrhosis. Three years after surgery the patient still has oesophageal varices but has not had recurrent bleeding. There was regression of intraduodenal varices.
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Fístula Arteriovenosa/complicaciones , Duodeno/irrigación sanguínea , Hemorragia Gastrointestinal/etiología , Hipertensión Portal/etiología , Arteria Mesentérica Inferior/anomalías , Venas Mesentéricas/anomalías , Várices/etiología , Anciano , Fístula Arteriovenosa/cirugía , Hemorragia Gastrointestinal/cirugía , Humanos , Masculino , Várices/cirugíaRESUMEN
A prospective study was performed in 67 male patients with cirrhosis, admitted in our Department during one year. Biliary lithiasis was found in 37% of patients. The occurrence of lithiasis was not related to age, weight or severity of liver disease. Seric total bilirubin was higher in lithiasic patients (p < 0.05). Apolipoprotein A1 levels were lower in those ones with lithiasis (p < 0.005). Apolipoprotein A1 was the only factor associated independently with the finding of lithiasis.
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Apolipoproteína A-I/sangre , Colelitiasis/epidemiología , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Biomarcadores , Colelitiasis/sangre , Humanos , Masculino , Persona de Mediana Edad , Portugal/epidemiología , Estudios ProspectivosRESUMEN
PURPOSE: We tested the hypothesis that polymerase chain reaction (PCR) quantitation of the enzyme thymidylate synthase (TS) within a primary adenocarcinoma of the stomach, has an inverse relationship to response and survival for patients who receive fluorouracil (5FU)-based chemotherapy. PATIENTS AND METHODS: Before systemic chemotherapy, the genetic expression of TS (TSmRNA level) was determined using a PCR method. Gene expression was calculated by determining the ratio between the amount of radiolabeled PCR product with the linear amplification range of the TS gene and the beta-actin gene. Chemotherapy consisted of two cycles of protracted infusion (PI) 5FU 200 mg/m2/d administered for 3 weeks with leucovorin 20 mg/m2/w. Cisplatin 100 mg/m2 was administered on day 1. RESULTS: Sixty-five patients with primary gastric cancer had a median TS mRNA level of 4.6 x 10(-3) (range, 0.9 to 20.1 x 10(-3)). Thirty-five percent of patients had measurable responses in their primary tumors. The mean gastric cancer TSmRNA level in responding and resistant patients is statistically significant (P < .001). The median survival time was 43+ months for treated patients with TSmRNA levels less than the median and 6 months for those with TS m-RNA levels greater than the median (P = .003). CONCLUSION: The genetic expression of TS (TSmRNA level) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer. Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor.
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Adenocarcinoma/enzimología , ARN Mensajero/metabolismo , Neoplasias Gástricas/enzimología , Timidilato Sintasa/biosíntesis , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Secuencia de Bases , Cisplatino/administración & dosificación , Etnicidad/genética , Femenino , Fluorouracilo/administración & dosificación , Gastroscopía , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Tasa de Supervivencia , Timidilato Sintasa/genéticaRESUMEN
A clinical trial for patients with measurable, disseminated colorectal cancer is being conducted to determine: (1) if intratumoral expression of thymidylate synthase (TS) affects response to protracted-infusion 5-fluorouracil (5FU); and (2) whether intratumoral expression of TS increases when clinical resistance is found after response to 5-FU. Polymerase chain reaction technology is employed to determine TS expression. Using beta-actin as an internal standard, TS expressions for 26 patients range from 0.5 x 10(-3) to 22.6 x 10(-3). Currently, 22 patients are evaluable for response and TS quantitation of their measurable tumour. 8 patients (36%) have had partial responses; 3 responding patients had been previously treated with 5-FU. A strong statistical association between TS expression and resistance to therapy has been found (P = 0.004). No patient with TS expression of 4.0 x 10(-3) or greater has responded. On average, patients previously treated with 5-FU have slightly higher levels of TS expression in their measurable tumours (P = 0.4). Whether responding patients will develop increased expressions of TS upon clinical progression of their cancer remains to be determined. Confirmation of these results in a larger cohort could lead to a scientific rationale for deciding upon specific therapy for patients with disseminated colorectal cancers.