Evaluación postratamiento locorregional y sistémico del carcinoma hepatocelular / Evaluating the response to locoregional and systemic treatment for hepatocellular carcinoma

La evaluación de la respuesta a los diferentes tratamientos aplicados es un factor decisivo en el manejo clínico de los pacientes con carcinoma hepatocelular. Con ella se logra determinar la eficacia del tratamiento y detectar de forma precoz la recidiva del tumor tratado o la aparición de nuevas lesiones que puedan ser candidatas a nuevos tratamientos. Cuando se aplican tratamientos locorregionales, que inducen necrosis, o terapias moleculares, que tienen efectos antiangiogénicos, las lesiones tratadas suelen presentar un cambio en su comportamiento por imagen. Cabe resaltar que no suelen presentar una disminución de su tamaño, al menos inicialmente, e incluso algunas lesiones pueden aparentemente aumentar de tamaño. Por ello es imprescindible conocer el mecanismo de acción de cada tratamiento utilizado y el espectro de imagen que pueden producir esos tratamientos en las distintas técnicas que se emplean en su valoración

Evaluating the response to different treatments is a decisive factor in the clinical management of patients with hepatocellular carcinoma because it can determine the efficacy of the treatment and because it can detect the recurrence of treated tumors or the appearance of new lesions that can be candidates for new treatments. When locoregional treatments that induce necrosis or molecular therapies are applied, the treated lesions usually change their behavior on imaging studies. It is important to point out that the size of the lesions does not usually decrease, at least initially, and some lesions can even appear to increase in size. For this reason, it is essential to know the mechanisms of action for each treatment applied and the spectrum of findings that these treatments can cause in the different imaging techniques used to assess the response

Evaluating the response to locoregional and systemic treatment for hepatocellular carcinoma. / Evaluación postratamiento locorregional y sistémico del carcinoma hepatocelular.

Evaluating the response to different treatments is a decisive factor in the clinical management of patients with hepatocellular carcinoma because it can determine the efficacy of the treatment and because it can detect the recurrence of treated tumors or the appearance of new lesions that can be candidates for new treatments. When locoregional treatments that induce necrosis or molecular therapies are applied, the treated lesions usually change their behavior on imaging studies. It is important to point out that the size of the lesions does not usually decrease, at least initially, and some lesions can even appear to increase in size. For this reason, it is essential to know the mechanisms of action for each treatment applied and the spectrum of findings that these treatments can cause in the different imaging techniques used to assess the response.

Gastrointestinal stromal tumors.

BACKGROUND: We reviewed radiologic features of gastrointestinal stromal tumors (GISTs) and correlated them with clinical and pathologic findings. METHODS: We investigated a series of 39 c-Kit-positive GISTs. Clinical and radiologic findings and management of these patients were recorded. RESULTS: Twenty women and 19 men (mean age 64 years) had histologically proved GIST. Tumor locations were the small bowel (n = 20), stomach (n = 14), rectum (n = 4), and omentum (n = l). Symptoms at presentation were most frequently gastrointestinal bleeding (n = 14) and abdominal pain (n = l1). Tumors were classified as very low risk (n = 2), low risk (n = 10), intermediate risk (n = 12), and high risk (n = 11). Ultrasonography, computed tomography, magnetic resonance, digital subtraction angiography, and barium series were used in the evaluation of these tumors. Most tumors were seen as well-delineated soft tissue masses with heterogeneous contrast enhancement. Necrosis, calcification, and ulceration were most commonly seen in large tumors that presented a more aggressive behavior. CONCLUSION: GISTs can arise anywhere in the gastrointestinal tract and present a great variety of clinical and radiologic features, depending mostly on size and location.

The kidney in paroxysmal nocturnal haemoglobinuria: MRI findings.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired stem-cell disorder characterized by defective haematopoiesis, which results in an increased sensitivity of the erythrocytes to complement-mediated intravascular haemolysis. Renal damage is infrequent but can produce chronic renal failure due cortical deposits of haemosiderin and microvascular thrombosis. MRI provides characteristic images of the kidneys that enable haemosiderin deposition to be diagnosed; in PNH, MRI typically shows reversed renal cortex-medulla differentiation on T(1) weighted images and substantial loss of cortical signal intensity on both T(1) and T(2) weighted images. We describe the MRI findings of renal cortical haemosiderosis occurring in four patients with PNH.

Magnetic resonance imaging of the intrauterine fetal genitourinary tract: normal anatomy and pathology.

Although ultrasonography (US) remains the most widely used diagnostic imaging modality for routine evaluation of the fetus, magnetic resonance (MR) imaging has become an invaluable complement to US in all cases in which additional information is desirable. While the ability of US to detect fetal abnormalities is limited in cases such as maternal obesity, oligohydramnios, and in certain fetal positions, MR using fast and ultrafast pulse sequences enables high-quality fetal images to be acquired regardless of the mother's physical condition or fetal position. Fetal genitourinary disorders are the most common intrauterine abnormalities detected by US, accounting for approximately 30% of all antenatally detected anomalies. Although they usually occur in isolation, these defects can form part of more complex syndromes or chromosomopathies, and MR is indicated to rule out associated abnormalities. In some severe genitourinary disorders, there is a severe deficit of amniotic fluid; these cases are associated with other fetal anomalies such as pulmonary hypoplasia and very poor prognosis. In other cases, the amniotic fluid is not compromised, yet the further detection, localization, and characterization of prenatal disorders will have an impact on postnatal follow-up. This article reviews the role of fetal MR in urogenital tract disorders.

Hepatic angiomyolipoma: progressive changes in size and tumor composition.

We report on 8 years of imaging and clinical follow-up of a confirmed hepatic angiomyolipoma (AML) undergoing notable growth over this period. The tumor grew considerably in the first 5 years, and its growth especially affected the fatty component; in the last 3 years, growth occurred more slowly. Radiologists should be aware that tumor growth of a hepatic AML can occur.

Primary biliary tract malignant melanoma: US, CT, and MR findings.

We report a case of primary biliary tract malignant melanoma occurring in a 47-year-old male. Ultrasonography and computed tomography showed multiple masses in the gallbladder and distal common bile duct that caused biliary tract dilatation. Magnetic resonance imaging showed that the polypoid masses in the gallbladder and common bile duct were of low signal intensity on T2-weighted images and of high signal intensity on unenhanced T1-weighted images.

Practice analysis for infection control and epidemiology in the new millennium.

BACKGROUND: The Certification Board of Infection Control and Epidemiology appointed an advisory committee to conduct a practice analysis (PA) of infection control professionals (ICPs) to identify current practices of ICPs. Results of the PA would assist in the development of a revised certification examination. METHODS: Five thousand seven hundred fifty-three questionnaires were distributed to ICPs in the United States and in Canada, as well as to a subsample of ICPs in other countries. Decision rules and criteria were applied to each identified task in the PA. RESULTS: A total of 1306 responses were available for analysis, for a 24% return rate. The majority of the respondents were certified in infection control, had a background as a registered nurse, and worked in a community hospital with 200 or fewer beds. Six major categories, with 135 tasks, were identified in the PA. The following 2 new categories were included: education and research and infection control aspects of employee health. CONCLUSIONS: The PA reflects current changes in the practice of infection prevention/control and applied epidemiology in the United States and Canada. The test specifications accepted for adoption by the Certification Board of Infection Control and Epidemiology will be used to build all examination forms for a certification program for ICPs.

Comparison of anti-PR3 capture and anti-PR3 direct ELISA for detection of antineutrophil cytoplasmic antibodies (ANCA) in long-term clinical follow-up of PR3-ANCA-associated vasculitis patients.

A total of 118 sera from 11 patients with anti-neutrophil cytoplasmic antibodies against proteinase-3- (PR3-ANCA) associated vasculitis were retrospectively screened by anti-PR3 capture and anti-PR3 direct ELISA tests. We studied the relationship between capture and direct ELISA scores and the clinical activity of PR3-ANCA-associated vasculitis patients during follow-up. We also studied the ability of the anti-PR3 capture ELISA to detect positive values of PR3-ANCA in clinical vasculitis relapses. Only capture ELISA presented a significant relationship (p < 0.05) with clinical activity of PR3-ANCA-associated vasculitis patients over time. Capture ELISA appears to be a reliable method for detecting clinical relapses in this group of patients. Our results indicate that the new capture ELISA test is more effective than direct ELISA in the follow-up of patients with PR3-ANCA-associated vasculitis and in the detection of relapses.

ELISA ANCA-GBM de detección rápida. Una herramienta de urgencia en el diagnóstico precoz de las glomerulonefritis rápidamente progresivas (gnrp) de tipo i y iii / The ANCA-GMB ELISA screening test: a rapid test for the diagnosis of rapide progressive glomerulonephritides

Las glomerulonefritis rápidamente progresivas (GNRP) de tipo I y III son formas de GNRP necrotizante asociadas a anticuerpos anti-membrana basal glomerular (anti-GBM) y a anticuerpos anticitoplasma del neutrófilo (ANCA) anti-proteinasa3 (anti-PR3) y anti-mieloperoxidasa (anti-MPO). Estas enfermedades tienen asociado una progresión rápida hacia la insuficiencia renal.En este estudio hemos comparado los ELISAs semicuantitativos para la detección de anticuerpos anti-GBM, ANCA anti-PR3 y anti-MPO y la técnica de inmunofluorescencia (IFI) con el ELISA rápido para la detección conjunta (en un tiempo de 30 minutos) de estos anticuerpos en pacientes con alta sospecha de GNRP. El valor diagnóstico de estos ELISAs semicuantitativos y de la técnica de IFI en el diagnóstico de pacientes con GNRP tipo I o III es conocido. El test estos de detección rápida no ha mostrado diferencias significativas con los resultados de ELISA anti-GBM, anti-PR3 o anti-MPO para los tres anticuerpos (p > 0,05). Asimismo, no se han encontrado diferencias significativas en los resultados del test rápido para anticuerpos anti-PR3 y anti-MPO respecto a los valores de IFI para C-ANCA y P-ANCA (p > 0,05). Su validez como herramienta diagnóstica de las GNRP tipo I y III comparada con los ELISAs semicuantitativos y la técnica de IFI ha sido, igualmente, confirmada.De los resultados de este estudio se desprende que el test de detección rápida es una herramienta tan útil como el ELISA semicuantitativo anti-GBM en el diagnóstico de GNRP tipo I y también lo es en el diagnóstico de GNRP tipo III comparado con las técnicas de IFI y ELISA semicuantitativo anti-PR3 o anti-MPO. Pero además, el test rápido tiene la ventaja añadida de procurar resultados en sólo 30 minutos y la comodidad de combinar tres resultados de tres anticuerpos diferentes en un solo test. (AU)

Cardiovascular risk factors and the long-term outcome of lupus nephritis.

We evaluated cardiovascular risk factors, morbidity and mortality in patients with lupus nephritis (LN). We prospectively studied 70 consecutive patients with LN, and 70 age- and sex-matched controls with systemic lupus erythematosus (SLE) but no evidence of nephropathy, from 1988 to 1998. Patients were evaluated at entry for hypertension, diabetes, hyperlipidaemia, smoking, menopause and antiphospholipid syndrome. The LN patients (64 women, 6 men) had a mean age of 35 years (SE 1.7, range 11-67). During the 10 years, 15 (21%) LN patients and 18 (25%) of the controls were lost to follow-up. Compared with controls, LN patients had a higher prevalence of hyperlipidaemia (44% vs. 2%, p<0.001), hypertension (44% vs. 9%, p<0.001) and antiphospholipid antibodies (45% vs. 22%, p=0.01) at study onset. At the last visit, 37 (67%) LN patients had normal plasma creatinine, 13 (24%) had renal failure and only five (9%) end-stage renal failure. Hyperlipidaemia (78% vs. 27%, p<0.001) and hypertension (67% vs. 32%, p=0.01) at study onset were associated with development of renal failure. Nine LN patients and one control died (16% vs. 2%, p=0.02). These patients showed more antiphospholipid syndrome (56% vs. 17%, p=0.03) and hyperlipidaemia (78% vs. 37%, p=0.03) at study onset. The main causes of death in LN patients were vascular complications (cardiovascular or cerebrovascular events) in five patients (four of whom had antiphospholipid antibodies) and sepsis in three.

Circulating soluble adhesion molecules in ANCA-associated vasculitis.

BACKGROUND: To evaluate whether changes in concentrations of soluble (s) E-selectin, sP-selectin, sL-selectin, intercellular adhesion molecule 1 (sICAM-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in patients with chronic renal failure (CRF). SUBJECTS AND METHODS: A sandwich ELISA was used to measure these soluble adhesion molecules in (i) sera from 20 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granulomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtained at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis. RESULTS: At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88+/-42 ng/ml, 437+/-184 ng/ml, 1720+/-1174 ng/ml respectively) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P<0.0001, P=0.002 and P=0.001 respectively). Serum sP-selectin values did not differ from those obtained in normal donors. In contrast, sL-selectin levels (940+/-349 ng/ml) were significantly lower in patients than those recorded in healthy controls (P<0.0001). A significant decrease in concentrations of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 was observed between active and remission phases (P<0.0001, P=0.002, P=0.001 and P=0.001 respectively). No significant differences were observed in sL-selectin levels between active and remission phases. sL-selectin concentrations (802+/-306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P<0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-selectin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negative correlation was established between creatinine and sL-selectin concentration. CONCLUSIONS: Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 and decreased levels of sL-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remission phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels between active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF suggests that the mechanism of clearance of these molecules is not renal.

[Rapid-detection GBM-ANCA ELISA. An emergency tool for the early diagnosis of type I and II rapidly progressive glomerulonephritis]. / ELISA ANCA-GBM de detección rápida. Una herramienta de urgencia en el diagnóstico precoz de las glomerulonefritis rápidamente progresivas (GNRP) de tipo I y III.

Rapidly progressive glomerulonephritides (RPGN) are forms of necrotizing glomerulonephritis associated with anti-glomerular basement membrane (anti-GBM) and anti-neutrophil cytoplasmic antibodies (ANCA) against the antigens proteinase-3 (anti-PR3) and myeloperoxidase (anti-MPO). RPGN have a course of rapid progression to renal failure. We compared the results from the semiquantitative ELISAs for anti-GMB antibodies, PR3-ANCA and MPO-ANCA and the indirect immunofluorescence technique (IIF) against a new rapid assay (30 minutes) for the same antibodies in patients with clinically suspected RPGN. The semiquantitative ELISAs for anti-GBM antibodies and PR3-ANCA and MPO-ANCA have a proven diagnostic significance in patients with RPGN I and III. There were no significant differences between the ANCA-GBM screening test and the results from the semiquantitative ELISAs (p > 0.05). We did not find significant differences between the results for PR3-ANCA and MPO-ANCA from the ANCA-GBM screening test with C-ANCA and P-ANCA IIF values (p > 0.05). We also corroborated that the ANCA-GBM screening test is a diagnostic tool for RPGN I and III as useful as the semiquantitative ELISAs and the IFF technique. The ANCA-GBM ELISA screening test is a tool as useful as the semiquantitative ELISA against anti-GBM antibodies for diagnosis of RPGN I. The comparison of the screening ELISA with the IIF technique and the semiquantitative ELISAs against PR3-ANCA and MPO-ANCA showed similar utility for diagnosis of RPGN III. The advantages of the new screening assay are that three antibodies are tested at the same time, yielding results in only 30 minutes.

Estatus epiléptico no convulsivo secundario a cefepima a dosis ajustadas en enfermos con insuficiencia renal crónica / Non-convulsive epileptic status after administration of cefepime in patients with advanced chronic renal failure

El síndrome febril es uno de los principales motivos de ingreso hospitalario en pacientes con insuficiencia renal crónica. En algunos casos se presentan sin focalidad clínica evidente y la falta de respuesta al tratamiento empírico inicial obliga al cambio por otros antibióticos de más amplio espectro. La disponibilidad de cefalosporinas de cuarta generación (cefepima) y la frecuencia creciente de resistencias microbianas a antibióticos más antiguos hace que el uso de estas sea cada día más frecuente en el medio hospitalario. Presentamos dos casos clínicos de estatus epiléptico no convulsivo en pacientes con insuficiencia renal que recibieron cefepima a dosis corregidas para el grado de función renal segón posología recomendada por el laboratorio. El cuadro neurológico debutó en forma de bradipsiquia, desorientación, déficit de atención y posterior aparición de movimientos mioclónicos. En los dos casos el electroencefalograma (EEG) presentaba un patrón compatible con estatus epiléptico no convulsivo. El cuadro clínico remitió y se normalizó el EEG en ambos casos tras la retirada del antibiótico. Una revisión de la literatura sobre la farmacocinética de cefepima indica que las dosis aconsejadas en la ficha técnica del fármaco son posíblemente demasiado elevadas en pacientes con insuficiencia renal avanzada. Concluimos que el tratamiento con cefepima en pacientes con insuficiencia renal avanzada puede desencadenar un estatus epiléptico no convulsivo. Es urgente que los estudios farmacocinéticos aclaren definitivamente la posología de este fármaco en este grupo de pacientes (AU)

Sonographic pattern of recessive polycystic kidney disease in young adults. Differences from the dominant form.

BACKGROUND: To study the sonographic pattern of autosomal recessive polycystic kidney disease (ARPKD) in early adulthood in order to identify imaging criteria to diagnose this disease and to distinguish between recessive and autosomal dominant polycystic kidney disease (ADPKD) in that age group. METHODS: An abdominal ultrasound was performed on four ARPKD subjects (with a mean age of 20.2) and on 33 ADPKD subjects in early adulthood (29 without renal failure with a mean age of 20.5, and four with renal failure with a mean age of 26.5). Linkage studies with ADPKD and ARPKD markers were compatible with the clinical diagnosis in all cases. RESULTS: The renal sonographic features in ARPKD subjects included multiple small cysts in a normal-sized kidney, increased cortical echogenicity and loss of corticomedullary differentiation. In ADPKD subjects without renal failure, sonographic features included few or multiple cysts of different sizes, in normal-sized kidneys in 22 out of 29 patients (75.8%), normal cortical echogenicity and conserved corticomedullary differentiation, except in patients with nephromegaly. All ADPKD subjects with renal failure had nephromegaly and loss of corticomedullary differentiation. The hepatic sonographic features in ARPKD patients included portal fibrosis and in some cases Caroli's disease, while in ADPKD patients a normal hepatic echostructure was detected in all but one case, in addition to simple hepatic cysts in a few cases. CONCLUSIONS: The evaluation of the sonographic features of the kidneys and those of the liver may help in the differential diagnosis between ARPKD and ADPKD in early adulthood.

Increased prevalence of polycystic kidney disease type 2 among elderly polycystic patients.

Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous, with at least three chromosomal loci (PKD1, PKD2, and PKD3) accounting for the disease. Mutations in the PKD2 gene, on the long arm of chromosome 4, are estimated to be responsible for 15% of the cases of ADPKD, based on linkage studies. PKD2 is a milder form of the disease, with a mean age of end-stage renal disease (ESRD) approximately 20 years later than PKD1. The object of this study is to determine the proportion of elderly patients with ADPKD with ESRD who harbor mutations in the PKD2 gene. We analyzed all exons and intron-exon boundaries of the PKD2 gene by single-strand conformation polymorphism analysis and silver staining technique in 46 patients with ADPKD who reached ESRD after the age of 63 years or were not yet undergoing renal replacement therapy (RRT) by that age. We performed exactly the same studies in a control group of 40 patients with ADPKD with unknown gene status aged younger than 63 years. In 22 patients, a mutation in the PKD2 gene was defined: 18 of 46 patients from the elderly group and 4 of 40 patients from the control group. We identified 14 different mutations: 4 nonsense mutations, 1 missense mutation, 5 small deletions, 2 insertions, 1 deletion of the whole PKD2 gene, and 1 splicing mutation. Five of these mutations previously were described by our group. Three of the mutations reported in the present study are recurrent. The prevalence of PKD2 disease among elderly patients with ADPKD undergoing RRT is 39.1%, almost three times the prevalence of the disease in the general ADPKD population.

Loss of heterozygosity in renal and hepatic epithelial cystic cells from ADPKD1 patients.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the commonest genetic diseases in man, affecting 1:1000 individuals in the Caucasian population. It is caused by mutations in the PKD1 or PKD2 genes. Recently, controversial data regarding the mutational mechanism underlying cyst initiation have been reported: genetic analyses have shown that second somatic mutations may lead to cyst formation (detected as microsatellite loss of heterozygosity, LOH, and point mutations), but immunohistochemical studies show strong immunoreactivity for polycystin in some cysts. In order to further characterise this matter we have analysed 211 cysts from seven different patients for LOH, we have detected a 13.3% LOH for PKD1. This loss was specific to PKD1 as no LOH was detected when other chromosomal regions were studied. Whenever linkage analysis has been possible, it has been proved that the lost allele corresponded to the wild-type. Our data supports previous results in the two-hit theory for ADPKD due to the large number of cysts studied. ADPKD would occur through a recessive cellular mechanism. The probability of cyst development would depend on the probability of mutation in the second allele. The different phenotypical expression of the same mutation reported in ADPKD could be due to the different tendency of inactivation in the second allele in each individual.

[Heterozygosity loss and somatic mutations in type I and II dominant autosomal renal polycystic kidney disease: evidence of a recessive mechanism at a cell level in cystogenesis]. / Estudio de pérdidas de heterozigosidad y mutaciones somáticas en la poliquistosis renal autosómica dominante tipos I y II: demostración de un mecanismo recesivo a nivel celular en la cistogénesis.

Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder mainly characterized by renal cyst formation. Cysts in ADPKD are focal in nature, since only a small fraction of nephrons become cystic. The hypothesis that a second hit may be required for cyst formation has been proposed. This hypothesis suggests that inactivation of the inherited wild-type allele by a somatic mutation triggers cyst formation. In some cases, this second hit eliminates the normal allele and the affected cells remain with a single allele, which is the inherited mutated copy, and we only visualize one allele after the amplification by polymerase chain reaction; this is called loss of heterozygosity (LOH). In this study we have analysed the DNA isolated from epitehlial cells from 164 cysts of 8 kidneys affected by ADPKD type I and 30 cysts form a kidney affected by ADPKD type II. We have demonstrated the presence of LOH in 20.1% of PKD1 cysts and in 10% of PKD2 cysts. We have also found eight other different mutations in PKD2 cysts without LOH; so the percentage of somatic mutations in the PKD2 kidney reaches 36.6% of cysts. In conclusion, our data suggest that a recessive mechanism at the cellular level is implicated in cyst formation in the PKD1 and the PKD2 disease. The loss of both copies of the gene triggers the proliferation of a single cell, resulting in the cyst formation.