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1.
Clin Lab ; 64(10): 1719-1730, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-30336540

RESUMEN

BACKGROUND: Although colonoscopy-based screening has proven to be highly effective in detecting colorectal cancer (CRC), participation rates remain disappointing. Development of CRC is associated with a number of genetic or somatic mutations. New, non-invasive stool tests are currently being developed based on the detection of these alterations. We investigated if a non-invasive stool assay can offer sufficient sensitivity and specificity to supplement colonoscopy-based screening. METHODS: We compared a combined stool assay, which incorporates fecal occult blood testing (FOBT), quantification of human DNA (hDNA) as well as detection of genetic mutations of KRAS and BRAF (Combined DNA stool assay), with commercially available FOBT and M2-PK tests in a multi-centric six-armed pre-clinical case cohort study. Seven hundred thirty-four patients were recruited prior to elective/screening colonoscopy or prior to surgery in case of a recent CRC diagnosis. According to clinical assessment and colonoscopy/histology results, the following groups were assigned: controls, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), hyperplastic polyps, adenomas, and CRC. Finally, 566 out of 734 patients (77.1%) were screened for CRC and overall gut status via colonoscopy, FOBT, M2-PK, with combined FOBT/M2-PK and the Combined DNA stool assay as described here. RESULTS: All sensitivities and specificities are measured against histologically confirmed results by colonoscopy. Confirmed sensitivities for detecting colorectal cancer were 68% with FOBT, 83% with M2-PK, 90% with combined FOBT and M2-PK, and 85% with the Combined DNA stool assay. Specificities were 96% with FOBT, 61% with M2-PK, 62% with combined FOBT and M2-PK, and 92% with the Combined DNA stool assay in the control group with no pathological findings during colonoscopy. CONCLUSIONS: The Combined DNA stool assay detects CRC with a significantly higher Youden Index than the other reviewed non-invasive screening options. The results also suggest that the Combined DNA stool assay represents a reliable assay for detecting colorectal cancer, sufficient to be recommended as a supplement to colonoscopy screening.


Asunto(s)
Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , ADN de Neoplasias/análisis , Detección Precoz del Cáncer/métodos , Heces/química , Sangre Oculta , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Neoplasias Colorrectales/genética , Femenino , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Sensibilidad y Especificidad
2.
Cochrane Database Syst Rev ; 1: CD006745, 2015 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-25620061

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common global cancer. When HCC is diagnosed early, interventions such as percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), or radiofrequency (thermal) ablation (RF(T)A) may have curative potential and represent less invasive alternatives to surgery. OBJECTIVES: To evaluate the beneficial and harmful effects of PEI or PAI in adults with early HCC defined according to the Milan criteria, that is, one cancer nodule up to 5 cm in diameter or up to three cancer nodules up to 3 cm in diameter compared with no intervention, sham intervention, each other, other percutaneous interventions, or surgery. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register (July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1946 to July 2014), EMBASE (1976 to July 2014), and Science Citation Index Expanded (1900 to July 2014). We handsearched meeting abstracts of six oncological and hepatological societies and references of articles to July 2014. We contacted researchers in the field. SELECTION CRITERIA: We considered randomised clinical trials comparing PEI or PAI versus no intervention, sham intervention, each other, other percutaneous interventions, or surgery for the treatment of early HCC regardless of blinding, publication status, or language. We excluded studies comparing RFA or combination of different interventions as such interventions have been or will be addressed in other Cochrane Hepato-Biliary Group systematic reviews. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, and extracted and analysed data. We calculated the hazard ratios (HR) for median overall survival and recurrence-free survival using the Cox regression model with Parmar's method. We reported type and number of adverse events descriptively. We assessed risk of bias by The Cochrane Collaboration domains to reduce systematic errors and risk of play of chance by trial sequential analysis to reduce random errors. We assessed the methodological quality with GRADE. MAIN RESULTS: We identified three randomised trials with 261 participants for inclusion. The risk of bias was low in one and high in two trials.Two of the randomised trials compared PEI versus PAI; we included 185 participants in the analysis. The overall survival (HR 1.47; 95% confidence interval (CI) 0.68 to 3.19) and recurrence-free survival (HR 1.42; 95% CI 0.68 to 2.94) were not statistically significantly different between the intervention groups of the two trials. Trial sequential analysis for the comparison PEI versus PAI including two trials revealed that the number of participants that were included in the trials were insufficient in order to judge a relative risk reduction of 20%. Data on the duration of hospital stay were available from one trial for the comparison PEI versus PAI showing a significantly shorter hospital stay for the participants treated with PEI (mean 1.7 days; range 2 to 3 days) versus PAI (mean 2.2 days; range 2 to 5 days). Quality of life was not reported. There were only mild adverse events in participants treated with either PEI or PAI such as transient fever, flushing, and local pain.One randomised trial compared PEI versus surgery; we included 76 participants in the analyses. There was no significant difference in the overall survival (HR 1.57; 95% CI 0.53 to 4.61) and recurrence-free survival (HR 1.35; 95% CI 0.69 to 2.63). No serious adverse events were reported in the PEI group while three postoperative deaths occurred in the surgery group.In addition to the three randomised trials, we identified one quasi-randomised study comparing PEI versus PAI. Due to methodological flaws of the study, we extracted only the data on adverse events and presented them in a narrative way.We found no randomised trials that compared PEI or PAI versus no intervention, best supportive care, sham intervention, or other percutaneous local ablative therapies excluding RFTA. We found also no randomised clinical trials that compared PAI versus other interventional treatments or surgery. We identified two ongoing randomised clinical trials. One of these two trials compares PEI versus surgery and the other PEI versus transarterial chemoembolization. To date, it is unclear whether the trials will be eligible for inclusion in this meta-analysis as the data are not yet available. This review will not be updated until new randomised clinical trials are published and can be used for analysis. AUTHORS' CONCLUSIONS: PEI versus PAI did not differ significantly regarding benefits and harms in people with early HCC, but the two included trials had only a limited number of participants and one trial was judged a high risk of bias. Thus, the current evidence precludes us from making any firm conclusions.There was also insufficient evidence to determine whether PEI versus surgery (segmental liver resection) was more effective, because conclusions were based on a single randomised trial. While some data from this single trial suggested that PEI was safer, the high risk of bias and the lack of any confirmatory evidence make a reliable assessment impossible.We found no trials assessing PEI or PAI versus no intervention, best supportive care, or sham intervention.There is a need for more randomised clinical trials assessing interventions for people with early stage HCC. Such trials should be conducted with low risks of systematic errors and random errors.


Asunto(s)
Ácido Acético/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Etanol/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Ácido Acético/efectos adversos , Administración Cutánea , Adulto , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Ablación por Catéter/métodos , Etanol/efectos adversos , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Carga Tumoral
3.
Liver Int ; 32(9): 1407-14, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22679906

RESUMEN

BACKGROUND/AIMS: Patients with cirrhosis are classified in a compensated and a decompensated stage. Portal hypertension is responsible for most of the complications of cirrhosis that mark the transition from compensated to decompensated cirrhosis. The objectives of this study were (a) to analyse survival of the different stages and substages of cirrhosis and (b) to examine the prognostic value of the hepatic venous pressure gradient (HVPG) at each of the stages. METHODS: A total of 729 patients with suspected cirrhosis underwent routine measurement of portal pressure and systemic haemodynamics between 11/1995 and 12/2004. The primary end-point of the study was death, collected until November 30th, 2006. Multivariable analysis was performed using two models to determine predictors of death at each stage. RESULTS: A total of 443 patients were included in the study. The 1-year mortality was 5.4% in compensated and 20.2% in decompensated patients. Compensated patients in stage 1 (no varices) had a longer survival than stage 2 patients (varices present) (P = 0.015). In decompensated patients, survival was not different between stage 3 (ascites, with or without varices) and stage 4 (variceal haemorrhage, with or without ascites). Age and HVPG (cut-off 10 mmHg) were independent predictors of death in compensated patients, whereas MELD was in decompensated patients. CONCLUSION: Survival rates and predictors of death are different between patients with compensated and decompensated cirrhosis. Unlike the Italian cohort staging system, ascites is a better stratifying clinical event than variceal haemorrhage in patients with decompensated cirrhosis. The presence of clinically significant portal hypertension has prognostic value in compensated cirrhosis.


Asunto(s)
Ascitis/diagnóstico , Várices Esofágicas y Gástricas/diagnóstico , Hipertensión Portal/diagnóstico , Cirrosis Hepática/diagnóstico , Presión Portal , Adolescente , Adulto , Anciano , Ascitis/complicaciones , Ascitis/mortalidad , Ascitis/fisiopatología , Niño , Preescolar , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/mortalidad , Femenino , Alemania/epidemiología , Venas Hepáticas/fisiopatología , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/mortalidad , Lactante , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Presión Portal/fisiología , Pronóstico , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Adulto Joven
4.
Gut ; 59(7): 963-8, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20581243

RESUMEN

BACKGROUND: The Model for End Stage Liver Disease (MELD) predicts mortality in end stage liver disease. Incorporation of serum sodium into the MELD may improve diagnostic accuracy in decompensated patients with ascites. However, other complications of cirrhosis are not reflected. This study investigates whether quantitative liver function tests predict survival and increase prognostic accuracy of the MELD. METHODS: 604 patients with suspected cirrhosis were staged clinically and haemodynamically. Galactose-elimination-capacity, sorbitol clearance, lidocaine metabolism and indocyanin green (ICG) half life were determined. Survival was the primary end point of the study. Prognostic effects of individual parameters were calculated using Cox regression models and ROC curves. RESULTS: 321 patients on standard pharmacological and endoscopic treatment (PET) and 74 patients undergoing transjugular portosystemic shunting (TIPS) were studied. Of all quantitative liver function tests, ICG half life was the most accurate in predicting survival. Upon incorporation into the MELD, it modified the score in patients with PET up to 35 points. Clinically relevant changes to the score, however, occurred in patients with a MELD score between 10 and 30, allowing an objective prognostic discrimination of individual survival based on laboratory liver function and blood flow. The MELD-ICG was validated in the second cohort of patients undergoing TIPS implantation. CONCLUSION: ICG had the highest predictive value of the examined tests. Its incorporation into the MELD adds an estimation of liver blood flow and renders the new score MELD-ICG more accurate in predicting survival in intermediate to advanced cirrhosis than the MELD and MELD-Na.


Asunto(s)
Cirrosis Hepática/diagnóstico , Fallo Hepático/etiología , Adulto , Anciano , Anciano de 80 o más Años , Colorantes , Métodos Epidemiológicos , Femenino , Semivida , Humanos , Verde de Indocianina , Circulación Hepática , Cirrosis Hepática/complicaciones , Pruebas de Función Hepática/métodos , Masculino , Persona de Mediana Edad , Pronóstico
5.
BMC Cancer ; 10: 457, 2010 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-20735834

RESUMEN

BACKGROUND: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. METHODS: The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky >or=60%/Child-Pugh

Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Inductores de Interferón/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Extractos del Timo/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/secundario , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Cuidados Paliativos , Placebos , Estudios Prospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
6.
Scand J Gastroenterol ; 45(4): 468-76, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20082593

RESUMEN

OBJECTIVE: Acute hepatic fat accumulation appears to be crucial for liver regeneration after partial hepatectomy. Since fatty acids in the liver are provided by catecholamine-induced lipolysis in the adipose tissue, we investigated whether beta-adrenergic blockade of lipolysis might affect liver regeneration. MATERIAL AND METHODS: Mice were treated with propranolol prior to partial hepatectomy. Subsequently, liver regeneration was evaluated histologically, by determination of the relative liver weight and the mitotic index at different time points after surgery. RESULTS: Liver mass restoration was delayed by propranolol, which was associated with a lower hepatic triglyceride content. Ki-67 labelling indicated that liver regeneration was attenuated by propranolol through inhibition of mitosis. Hepatocytes were arrested in the G1 phase of the cell cycle, as shown by the expression of G1-related proteins such as proliferating cell nuclear antigen, cyclin D1 and cyclin-dependent kinase-2, and underwent apoptosis as indicated by detection of poly(adenosine diphosphate-ribose) polymerase fragments. beta-adrenergic blockade of the host animal did not provide transplanted hepatocytes with a growth advantage over host cells. CONCLUSION: Impairment of liver regeneration by propranolol is related to the inhibition of acute hepatic fat accumulation and to a predisposition of hepatocytes to apoptosis.


Asunto(s)
Hígado Graso/fisiopatología , Regeneración Hepática/efectos de los fármacos , Propranolol/farmacología , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Ciclo Celular , Fase G1 , Hepatectomía/métodos , Hepatocitos/metabolismo , Hepatocitos/trasplante , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL
7.
Cochrane Database Syst Rev ; (3): CD004064, 2010 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-20238327

RESUMEN

BACKGROUND: Gastric cancer currently ranks second in global cancer mortality. Most patients are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. Apart from supportive care and palliative radiation to localized (e.g. bone) metastasis, systemic chemotherapy is the only treatment option available in this situation. OBJECTIVES: To assess the efficacy of chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapy regimens in advanced gastric cancer. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE up to March 2009, reference lists of studies, and contacted pharmaceutical companies and national and international experts. SELECTION CRITERIA: Randomised controlled trials on systemic intravenous chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapies in advanced gastric cancer. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. MAIN RESULTS: Thirty five trials, with a total of 5726 patients, have been included in the meta-analysis of overall survival. The comparison of chemotherapy versus best supportive care consistently demonstrated a significant benefit in overall survival in favour of the group receiving chemotherapy (hazard ratios (HR) 0.37; 95% confidence intervals (CI) 0.24 to 0.55, 184 participants). The comparison of combination versus single-agent chemotherapy provides evidence for a survival benefit in favour of combination chemotherapy (HR 0.82; 95% CI 0.74 to 0.90, 1914 participants). The price of this benefit is increased toxicity as a result of combination chemotherapy. When comparing 5-FU/cisplatin-containing combination therapy regimens with versus without anthracyclines (HR 0.77; 95% CI 0.62 to 0.95, 501 participants) and 5-FU/anthracycline-containing combinations with versus without cisplatin (HR 0.82; 95% CI 0.73 to 0.92, 1147 participants) there was a significant survival benefit for regimens including 5-FU, anthracyclines and cisplatin. Both the comparison of irinotecan versus non-irinotecan (HR 0.86; 95% CI 0.73 to 1.02, 639 participants) and docetaxel versus non-docetaxel containing regimens (HR 0.93; 95% CI 0.75 to 1.15, 805 participants) show non-significant overall survival benefits in favour of the irinotecan and docetaxel-containing regimens. AUTHORS' CONCLUSIONS: Chemotherapy significantly improves survival in comparison to best supportive care. In addition, combination chemotherapy improves survival compared to single-agent 5-FU. All patients should be tested for their HER-2 status and trastuzumab should be added to a standard fluoropyrimidine/cisplatin regimen in patients with HER-2 positive tumours. Two and three-drug regimens including 5-FU, cisplatin, with or without an anthracycline, as well as irinotecan or docetaxel-containing regimens are reasonable treatment options for HER-2 negative patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Antraciclinas/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Cisplatino/administración & dosificación , Docetaxel , Fluorouracilo/administración & dosificación , Humanos , Irinotecán , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Gástricas/mortalidad , Taxoides/administración & dosificación
8.
Cochrane Database Syst Rev ; (3): CD006745, 2009 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-19588401

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common global cancer. When HCC is detected early, interventions such as percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), and radiofrequency thermal ablation (RFTA) have curative potential and represent low invasive alternatives to surgery. The role of PEI or PAI has not been addressed in a systematic review. OBJECTIVES: To evaluate the beneficial and harmful effects of PEI or PAI in adults with early HCC. SEARCH STRATEGY: A systematic search was performed in The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and ISI Web of Science in May 2009. Meeting abstracts of six oncological and hepatological societies (ASCO, ESMO, ECCO, AASLD, EASL, APASL) and references of articles were handsearched. Researchers in the field were contacted. SELECTION CRITERIA: Randomised trials comparing PEI or PAI with no intervention, sham intervention, other percutaneous interventions or surgery for the treatment of early HCC were considered regardless of blinding, publication status, or language. Studies comparing RFTA or combination treatments were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion, and extracted and analysed data. The hazard ratios for median overall survival and recurrence-free survival were calculated using the Cox regression model with Parmar's method. Type and number of adverse events were reported descriptively. MAIN RESULTS: Three randomised trials with a total of 261 patients were eligible for inclusion. The risk of bias was high in all trials. Two of the trials compared PEI with PAI. Overall survival (HR 1.47; 95% confidence interval (CI) 0.68 to 3.19) and recurrence-free survival (HR 1.42; 95% CI 0.68 to 2.94) were not significantly different. Data on the duration of hospital stay were inconclusive. Data on quality of life were not available. There were only mild adverse events in both treatment modalities.The other trial compared PEI with surgery. There was no significant difference in overall survival (HR 1.57; 95% CI 0.53 to 4.61) and recurrence-free survival (HR 1.35; 95% CI 0.69 to 2.63). No serious adverse events were reported in the PEI group. Three postoperative deaths occurred in the surgery group. AUTHORS' CONCLUSIONS: PEI and PAI does not differ significantly regarding benefits and harms in patients with early HCC, but only a limited number of patients have been examined and the bias risk was high in all trials. There is also insufficient evidence to determine whether PEI or segmental liver resection is more effective, although PEI may seem safer.


Asunto(s)
Ácido Acético/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Etanol/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Ácido Acético/efectos adversos , Administración Cutánea , Adulto , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Ablación por Catéter/métodos , Etanol/efectos adversos , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto
9.
BMC Cancer ; 8: 72, 2008 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-18366627

RESUMEN

BACKGROUND: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. METHODS: 44 patients (84 % male, median age 69 years) not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. RESULTS: Median survival was 11.5 months (95% CI 7.9-15.0) with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01), a low score in the Okuda- and CLIP-classification (p < 0.001) or a low AFP-level (p < 0.001) were associated with better survival, but not therapy modalities other than thymostimulin (p = 0.1) or signs of an invasive HCC phenotype such as vascular invasion (p = 0.3) and metastases (p = 0.1). The only variables independently related to survival in the Cox's regression model were Okuda stage and presence of liver cirrhosis (p < 0.01) as well as response to thymostimulin (p < 0.05). Of 39/44 patients evaluable for response, two obtained complete responses (one after concomitant radiofrequency ablation), five partial responses (objective response 18%), twenty-four stable disease (tumor control rate 79%) and eight progressed. Median progression-free survival was 6.4 months (95% CI 0.8-12). Grade 1 local reactions following injection were the only side effects. CONCLUSION: Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage) in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept. TRIAL REGISTRATION: Current Controlled Trials ISRCTN29319366.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Extractos del Timo/uso terapéutico , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Modelos de Riesgos Proporcionales , Análisis de Regresión , Extractos del Timo/metabolismo , Factores de Tiempo , Resultado del Tratamiento
10.
Methods Inf Med ; 57(S 01): e92-e105, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-30016815

RESUMEN

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on the German Medical Informatics Initiative. "Smart Medical Information Technology for Healthcare (SMITH)" is one of four consortia funded by the German Medical Informatics Initiative (MI-I) to create an alliance of universities, university hospitals, research institutions and IT companies. SMITH's goals are to establish Data Integration Centers (DICs) at each SMITH partner hospital and to implement use cases which demonstrate the usefulness of the approach. OBJECTIVES: To give insight into architectural design issues underlying SMITH data integration and to introduce the use cases to be implemented. GOVERNANCE AND POLICIES: SMITH implements a federated approach as well for its governance structure as for its information system architecture. SMITH has designed a generic concept for its data integration centers. They share identical services and functionalities to take best advantage of the interoperability architectures and of the data use and access process planned. The DICs provide access to the local hospitals' Electronic Medical Records (EMR). This is based on data trustee and privacy management services. DIC staff will curate and amend EMR data in the Health Data Storage. METHODOLOGY AND ARCHITECTURAL FRAMEWORK: To share medical and research data, SMITH's information system is based on communication and storage standards. We use the Reference Model of the Open Archival Information System and will consistently implement profiles of Integrating the Health Care Enterprise (IHE) and Health Level Seven (HL7) standards. Standard terminologies will be applied. The SMITH Market Place will be used for devising agreements on data access and distribution. 3LGM2 for enterprise architecture modeling supports a consistent development process.The DIC reference architecture determines the services, applications and the standardsbased communication links needed for efficiently supporting the ingesting, data nourishing, trustee, privacy management and data transfer tasks of the SMITH DICs. The reference architecture is adopted at the local sites. Data sharing services and the market place enable interoperability. USE CASES: The methodological use case "Phenotype Pipeline" (PheP) constructs algorithms for annotations and analyses of patient-related phenotypes according to classification rules or statistical models based on structured data. Unstructured textual data will be subject to natural language processing to permit integration into the phenotyping algorithms. The clinical use case "Algorithmic Surveillance of ICU Patients" (ASIC) focusses on patients in Intensive Care Units (ICU) with the acute respiratory distress syndrome (ARDS). A model-based decision-support system will give advice for mechanical ventilation. The clinical use case HELP develops a "hospital-wide electronic medical record-based computerized decision support system to improve outcomes of patients with blood-stream infections" (HELP). ASIC and HELP use the PheP. The clinical benefit of the use cases ASIC and HELP will be demonstrated in a change of care clinical trial based on a step wedge design. DISCUSSION: SMITH's strength is the modular, reusable IT architecture based on interoperability standards, the integration of the hospitals' information management departments and the public-private partnership. The project aims at sustainability beyond the first 4-year funding period.


Asunto(s)
Atención a la Salud , Tecnología de la Información , Algoritmos , Gestión Clínica , Comunicación , Sistemas de Apoyo a Decisiones Clínicas , Registros Electrónicos de Salud , Almacenamiento y Recuperación de la Información , Unidades de Cuidados Intensivos , Modelos Teóricos , Fenotipo , Políticas
11.
Z Arztl Fortbild Qualitatssich ; 101(8): 564-76, 2007.
Artículo en Alemán | MEDLINE | ID: mdl-18225408

RESUMEN

The Medical School of Halle has fundamentally restructured the university hospital's outpatient clinics. This required a detailed analysis of costs, income, and organization, as well as a prospective survey. In a representative month, more than 15,000 consultations were documented. Of all visits, 9% were part of clinical trials, and 19% part of the teaching and training of students and young doctors. 52% of all appointments were follow-up consultations. Operative and non-operative specialties as well as general and specialist consultations displayed considerable differences. Clinics with a high rate of follow-up consultations attended to fewer trial participants than others. In comparison to a district covered by statutory health insurance physicians the proportion of oncological diagnoses in the university hospital outpatient clinics was markedly higher. Costs for the different specialties' outpatient clinics varied significantly; a positive correlation was noted between the percentage of oncological diagnoses and secondary costs. The outpatient clinics' commitment to the outpatient care of cancer patients exceeds by far the scientific focus of the Medical School of Halle and contributes greatly to the provision of regional health care services. Within the scope of the project, the annual faculty allowances to the outpatient clinics were reduced by 25%. Since 2003, 60% of the remaining total allowances have been made available to the departments as an output-related grant. It was crucial to the acceptance of this budgeting that the expenses saved were dedicated to the support of young scientists, that the budgeting was comprehensible and that scientific achievements and in future also high quality teaching will continue to help regain some of the money "lost".


Asunto(s)
Servicio Ambulatorio en Hospital/economía , Servicio Ambulatorio en Hospital/normas , Presupuestos , Ensayos Clínicos como Asunto , Alemania , Hospitales Universitarios/economía , Hospitales Universitarios/normas , Humanos
12.
Artículo en Inglés | MEDLINE | ID: mdl-16997160

RESUMEN

Chemotherapy significantly improves survival in comparison to best supportive care in patients with metastasised gastric cancer. In patients for whom a three-drug-combination is considered as the treatment of choice, ECF (epirubicin, cisplatin and 5-FU as a continuous infusion) should be regarded as standard of care. However, results for ECF have been challenged by the recently presented REAL-2-trial, which demonstrated a significant survival benefit for EOX (epirubicin, oxaliplatin, capecitabine) over ECF. Adjuvant 5-FU-based chemoradiation should be discussed in patients with inadequate lymphadenectomy, but is not internationally accepted as standard of care: whether patients with adequate lymhphadenectomy benefit from adjuvant chemoradiotherapy is currently unclear. According to the results of the UK MAGIC trial, perioperative treatment with ECF (3 cycles prior to and post surgery) results in a significantly reduced risk of death for patients with resectable gastric cancer as compared to surgery alone. Neo-adjuvant chemotherapy has the ability to downsize gastric tumours and appears to improve R0-resection rates, but its potential to improve overall survival is still unclear.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Humanos , Estadificación de Neoplasias , Neoplasias Gástricas/patología , Resultado del Tratamiento
13.
Cell Transplant ; 14(7): 497-506, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16285258

RESUMEN

Although ex vivo culture of hepatocytes is known to impair functionality, it may still be considered as desirable to propagate or manipulate them in culture prior to transplantation into the host liver. The aim of this study was to clarify whether rat hepatocytes cultured over different periods of time proliferate and retain their hepatocyte-specific functions following transplantation into the recipient liver. Rat hepatocytes were cultured under serum-free conditions in the presence of hepatocyte and epidermal growth factors. Cells derived from wild-type donor livers were transplanted into the livers of CD26-deficient rats. Cell proliferation and the expression of hepatocyte-specific markers were determined before and after transplantation. Cell number increased threefold over a culture period of 10 days. The expression of connexin 32 and phosphoenolpyruvate carboxykinase declined over time, indicating the loss of hepatocyte-specific functions. Hepatocytes cultured over 4 or 7 days and then transplanted proliferated in the host parenchyma. The transplanted cells expressed connexin 32, cytokeratin 18, and phosphoenolpyruvate carboxykinase, indicating the differentiated phenotype. The loss of hepatocyte-specific functions during culture may be restored after transplantation, suggesting that the proper physiological environment is required to maintain the differentiated phenotype.


Asunto(s)
Trasplante de Células/métodos , Hepatocitos/química , Hepatocitos/citología , Hígado/citología , Animales , Proliferación Celular , Células Cultivadas , Conexinas/metabolismo , Medio de Cultivo Libre de Suero , Dipeptidil Peptidasa 4/metabolismo , Estudios de Factibilidad , Hepatocitos/trasplante , Queratinas/metabolismo , Ratones , Ratones Noqueados , Fosfoenolpiruvato Carboxilasa/metabolismo , Ratas , Ratas Wistar , Factores de Tiempo , Proteína beta1 de Unión Comunicante
15.
Med Klin (Munich) ; 100(10): 650-5, 2005 Oct 15.
Artículo en Alemán | MEDLINE | ID: mdl-16220253

RESUMEN

BACKGROUND: Transplantation of hepatocytes is considered a promising technology for the cell therapy of liver diseases. Cells are isolated from donor livers, which are not allocated for organ transplantation and transplanted into the liver of a suitable recipient. Ideally, the transplanted cells functionally replace the hepatocytes of the diseased organ and restore its metabolic capacity either permanently or for a period of bridging to organ transplantation. METHODS AND RESULTS: Although about 50 cases of clinical hepatocyte transplantation have been documented, therapeutic benefit is doubtful, and the reasons for this are largely unknown. Minor quality of the transplanted cells isolated from marginal donor livers may be a major cause. Therefore, animal models have been established, which enable scientists to develop novel procedures of hepatocyte transplantation and to specifically study the mechanisms of hepatocyte integration in the host liver. Hopefully, results generated in animal models will set the basis for the design of novel procedures of hepatocyte transplantation individualized to the underlying disease in order to provide a growth advantage for donor over host cells. PERSPECTIVES: The plasticity of stem cells and their proliferative potential is the basis for current efforts to generate stem cell-derived hepatocytes of transplantation quality for the treatment of liver diseases.


Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Hepatocitos/trasplante , Hepatopatías/terapia , Animales , Conexinas/genética , Criopreservación , Hepatocitos/patología , Humanos , Hepatopatías/genética , Hepatopatías/patología , Regeneración Hepática/genética , Trasplante de Hígado/patología
16.
Am J Clin Nutr ; 77(5): 1269-77, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12716682

RESUMEN

BACKGROUND: Homocysteine metabolism may be impaired in chronic liver disease, possibly contributing to fibrogenesis and disease complications. OBJECTIVE: The goal was to investigate the prevalence and determinants of basal and postprandial hyperhomocysteinemia in patients with chronic liver disease and after orthotopic liver transplantation (OLT). DESIGN: This was a cross-sectional study of 323 patients with chronic liver disease (93 with hepatitis, 8 with fatty liver, 168 with cirrhosis, and 54 after OLT) and 25 healthy control subjects. Portohepatovenous gradients of total homocysteine (tHcy) and methionine and postload methionine and tHcy kinetics before and after 10 d of supplementation with folate plus vitamin B-6 were investigated in subgroups. RESULTS: Basal hyperhomocysteinemia was observed in all patient groups (34% of patients with hepatitis, 50% with fatty liver, 54% with cirrhosis, and 52% after OLT). It was more frequently seen in patients with elevated plasma creatinine concentrations and at advanced stages of liver disease. Mean plasma folate was normal in patients with liver disease, but vitamin B-12 was elevated in cirrhosis and vitamin B-6 was low after OLT. There were significant negative associations between tHcy and folic acid or vitamin B-12 concentrations in control subjects and in patients with hepatitis and after OLT. No systematic association between portohepatovenous differences in tHcy and methionine concentrations was found. Cirrhosis was accompanied by impaired methionine clearance. After vitamin supplementation, the area under the tHcy curve improved in cirrhosis at nearly unchanged basal tHcy concentrations. CONCLUSIONS: Basal hyperhomocysteinemia is seen in approximately 50% of patients with cirrhosis and after OLT. Basal tHcy concentrations do not change significantly after supplementation with folate and vitamin B-6, but postprandial Hcy metabolism improves.


Asunto(s)
Homocisteína/sangre , Hiperhomocisteinemia/epidemiología , Hepatopatías/sangre , Trasplante de Hígado , Metionina/sangre , Adulto , Área Bajo la Curva , Estudios de Casos y Controles , Enfermedad Crónica , Creatinina/sangre , Estudios Transversales , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/sangre , Homocisteína/metabolismo , Humanos , Hiperhomocisteinemia/metabolismo , Hepatopatías/tratamiento farmacológico , Masculino , Tasa de Depuración Metabólica , Metionina/administración & dosificación , Metionina/metabolismo , Persona de Mediana Edad , Vitamina B 12/sangre , Vitamina B 6/administración & dosificación , Vitamina B 6/sangre
17.
Z Arztl Fortbild Qualitatssich ; 96(4): 233-8, 2002 May.
Artículo en Alemán | MEDLINE | ID: mdl-12068740

RESUMEN

Crohn's disease is still an incurable affliction: While various pathogenic mechanisms have been elucidated in detail, the etiology remains undetected. Conservative medical management is the mainstay of treatment with corticosteroids and azathioprin as pivotal drugs. Aminosalicylates are of minor importance. Infliximab may be effective for individual patients as a third line of treatment after failure of classical immunosuppression or when a rapid response is mandatory in a corticosteroid-resistant situation. Its long-term efficacy and safety in the treatment of fistulae is unknown. Antibiotics and nutritional measures may be of help in certain clinical conditions. Satisfactory means of maintaining remission in inactive patients is not available to date. Psychotherapy may be useful in helping patients to cope but does not significantly affect the course of the disease. The guidelines presented here are based on a consensus developed by the Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten in 1996 (26), updated in December 2001 (to be published) on the basis of recent randomized trials and meta-analyses.


Asunto(s)
Enfermedad de Crohn/terapia , Enfermedades del Sistema Digestivo/terapia , Humanos , Enfermedades Metabólicas/terapia , Guías de Práctica Clínica como Asunto , Garantía de la Calidad de Atención de Salud , Sociedades Médicas
18.
BMJ Case Rep ; 20092009.
Artículo en Inglés | MEDLINE | ID: mdl-22125582

RESUMEN

Budd-Chiari syndrome and membranous obstruction of the inferior vena cava frequently result in the development of mostly benign hepatic lesions. In cases of membranous obstruction of the inferior vena cava, which is prevalent mostly in the East, these lesions often progress to hepatocellular carcinoma. In contrast, malignant transformation has not yet been recognised in patients with isolated hepatic vein thrombosis. We report the case of a 37-year-old male Caucasian who presented with acute Budd-Chiari syndrome without involvement of the inferior vena cava. Despite porto-caval shunting, a hepatocellular carcinoma developed within several months. Three hepatic lesions were treated by radiofrequency thermal ablation until liver transplantation was performed. This report emphasises the possibility of malignant transformation of regenerative nodules in patients with disturbed hepatic perfusion in general. Physicians must be aware of this when assessing regenerative nodules, especially as no unambiguous predictors for the development of hepatocellular carcinoma have been identified so far.

19.
Eur J Gastroenterol Hepatol ; 20(10): 971-7, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18787463

RESUMEN

BACKGROUND: Capsule endoscopy (CE) sensitively detects the bleeding source in the small bowel. However, the influence of CE on long-term outcome is not well established. METHODS: In five tertiary hospitals, all CE investigations were retrospectively identified dating back to 3 years. Patients with intestinal bleeding and negative bidirectional endoscopy were included, and relapse of bleeding was recorded. RESULTS: A bleeding source was detected in 219 of 285 patients (76.8%); CE provided the diagnosis in 175 of 219 (79.9%) and other, repeated investigations in 44 cases (20.1%). Follow-up (mean+/-SD=20.7+/-9.4 months) in 240 patients identified rebleeding in 65 (27.1%), and readmission to a hospital in 42 (17.5%). Hospital readmission was most frequent in patients with angiectasias (31.3%, relative risk (RR)=5.0; 95% confidence interval (CI)=2.4-10.4). Other risk factors included patients being older than 60 years of age (RR=3.8; 95% CI=1.5-9.5), and anticoagulant medication (RR=3.0; 95% CI=1.5-6.0). Therapeutic measures had a mean recurrence rate of 3.7% in surgical candidates (Meckel's diverticulum, tumor), 40% in endoscopically treated and 16% in medically treated patients. In case all the detected angiectasias had been cauterized, the relapse rate was low (11.8%), but in incompletely treated patients, it was high (85.7%). Bleeding relapse was never lethal. CONCLUSION: CE guides therapeutic measures and predicts the risk of recurrent bleeding in small intestinal bleeding. High risk of rebleeding in angiectasias is significantly reduced by the cauterization of all demonstrable lesions.


Asunto(s)
Endoscopía Capsular , Hemorragia Gastrointestinal/patología , Enfermedades Intestinales/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Endoscopios en Cápsulas/efectos adversos , Endoscopía Capsular/efectos adversos , Niño , Femenino , Hemorragia Gastrointestinal/etiología , Neoplasias Gastrointestinales/patología , Humanos , Enfermedades Intestinales/etiología , Intestino Delgado , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Readmisión del Paciente , Pronóstico , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Úlcera Gástrica/patología , Resultado del Tratamiento
20.
J Hepatol ; 47(5): 642-50, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17869373

RESUMEN

BACKGROUND/AIMS: The value of paper-pencil tests and West-Haven-criteria for assessment of low-grade hepatic encephalopathy under conditions of a randomized, double-blind, placebo-controlled, clinical trial was evaluated in a cohort of 217 cirrhotics. METHODS: Patients were graded at least twice clinically for severity of hepatic encephalopathy and tested concomitantly with a recommended psychometric test battery. RESULTS: Re-evaluation of the study documentation showed that at study entry 33% and during the study even 50% of the patients were wrongly allocated to minimal or overt hepatic encephalopathy. Despite the participating physicians' training, 31% of the number-connection-tests-A, 20% of the number-connection-tests-B and 28% of the line-tracing-test were in retrospect considered invalid by an independent psychologist. Neither the Portosystemic-Encephalopathy-Syndrome (PSE) test nor the Psychometric-Hepatic-Encephalopathy-Sum (PHES)-score reliably picked up clinical improvement in the individual patient. Although these test scores could statistically differentiate between patients with minimal and overt hepatic encephalopathy, the clinical classification of individual patients into one of the groups will have a high rate of error. The PHES-Score was less balanced than the score derived from the PSE-Syndrome-Test. CONCLUSIONS: Inaccuracies in conducting paper-pencil tests together with the subjectivity and incorrectness of clinical HE-grading question the usefulness of West-Haven-criteria and paper-pencil tests including related scores for quantification of low-grade HE at least in multicenter approaches.


Asunto(s)
Evaluación de la Discapacidad , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/psicología , Hepatopatías/complicaciones , Pruebas Neuropsicológicas/normas , Psicometría/métodos , Estudios de Cohortes , Diagnóstico Diferencial , Método Doble Ciego , Estudios de Evaluación como Asunto , Fibrosis/complicaciones , Encefalopatía Hepática/fisiopatología , Humanos , Estudios Longitudinales , Placebos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Prueba de Secuencia Alfanumérica
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