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BACKGROUND: POD1UM-203, an open-label, multicenter, phase II study, evaluated retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in patients with selected solid tumors where immune checkpoint inhibitor therapies have previously shown efficacy. PATIENTS AND METHODS: Eligible patients (≥18 years) had measurable disease and included unresectable or metastatic melanoma, treatment-naive metastatic non-small-cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression (tumor proportion score ≥50%), cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (UC) with PD-L1 expression (combined positive score ≥10%), or treatment-naive locally advanced/metastatic clear-cell renal cell carcinoma (RCC). Retifanlimab 500 mg was administered intravenously every 4 weeks as a 30-min infusion. The primary endpoint was investigator-assessed overall response rate. RESULTS: Overall, 121 patients (35 melanoma, 23 NSCLC, 29 UC, 34 RCC) were enrolled and treated. The overall response rate [95% confidence interval (CI)] was 40.0% (23.9-57.9) in the melanoma cohort, 34.8% (16.4-57.3) in the NSCLC cohort, 37.9% (20.7-57.7) in the UC cohort, and 23.5% (10.7-41.2) in the RCC cohort. Median duration of response was 11.5 months (95% CI 2.2-not reached) in the UC cohort, and was not reached in the other cohorts. Retifanlimab safety was consistent with previous experience for PD-(L)1 inhibitors. CONCLUSIONS: Retifanlimab demonstrated durable antitumor activity in patients with melanoma, NSCLC, UC, or RCC. The efficacy and safety of retifanlimab were as expected for a PD-(L)1 inhibitor. These data support further study of retifanlimab in solid tumors.
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Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Renales , Carcinoma de Células Transicionales , Neoplasias Pulmonares , Melanoma , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Renales/tratamiento farmacológico , Antígeno B7-H1 , Melanoma/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéuticoRESUMEN
Congenital diaphragmatic hernia is a rare condition caused by a malformation in the diaphragm that is usually diagnosed in newborns, infants and children. Sometimes it can be incidentally identified in adults. Once the diagnosis is made, surgery is indicated to avoid the risk of life-threatening complications of herniated viscera. Traditional approaches include laparotomy or thoracotomy or both; in the last decades minimally invasive techniques have proved to be a safe alternative to the open approach but only few cases of robotic hernia repair have been described so far, the most with a combined thoracic-abdomen approach. We report a case of an 18-year-old female presenting with abdominal pain due to a giant left-sided anterior diaphragmatic hernia (Larrey-type) that was repaired using a robotic-assisted laparoscopic approach with mesh placement. The hernia contents included gastric body and fundus, duodenum, jejunum, ileus, cecum, right colon and mesentery; spleen and pancreas were rotated and dislocated anteriorly. The outcome was unremarkable, with no major post-operative complications and no signs of long-term recurrence. The robotic approach seems to be a valid option for the treatment of diaphragmatic hernias, improving post-operative outcome and providing surgeon better visualization, greater precision and enhanced dexterity in a confined space.
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BACKGROUND: The principles for maintenance intravenous fluid prescription in children were developed in the 1950s. These guidelines based on the use of hypotonic solutions have been challenged regularly for they seem to be associated with an increased risk of hospital-acquired hyponatremia. CASE PRESENTATION: We report the case of a 4-week-old Caucasian child admitted for acute bronchiolitis who received hypotonic maintenance fluids and developed severe hyponatremia (94 mmol/L) with hyponatremic encephalopathy. CONCLUSION: This clinical situation can serve as a reminder of the latest recommendations from the American Academy of Pediatrics regarding the use of intravenous fluids that promote the use of isotonic fluids in children.
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Hiponatremia , Niño , Fluidoterapia , Humanos , Hiponatremia/etiología , Hiponatremia/terapia , Soluciones Hipotónicas/efectos adversos , Infusiones Intravenosas , Soluciones IsotónicasRESUMEN
BACKGROUND: Checkpoint inhibitors in melanoma can lead to self-immune side-effects such as vitiligo-like depigmentation (VLD). Beyond the reported association with favorable prognosis, there are limited data regarding VLD patient features and their echo on the therapeutic outcomes. METHODS: To assess the association between VLD and a series of clinical and biological features as well as therapeutic outcomes, we built an observational cohort study by recruiting patients who developed VLD during checkpoint inhibitors. RESULTS: A total of 148 patients from 15 centers (101 men, median age 66 years, BRAF mutated 23%, M1c 42%, Eastern Cooperative Oncology Group (ECOG) status 0/1 99%, normal lactate dehydrogenase 74%) were enrolled. VLD was induced by ipilimumab, programmed cell death-1 (PD-1) inhibitors, and their combination in 32%, 56%, and 12%, respectively. The median onset was 26 weeks and it was associated with other skin and nonskin toxicities in 27% and 28%, respectively. After 3 years of VLD onset, 52% (95% confidence interval 39% to 63%) were progression free and 82% (95% confidence interval 70% to 89%) were still alive. The overall response rate was 73% with 26% complete response. Univariable analysis indicated that BRAF V600 mutation was associated with a better overall survival (P = 0.028), while in multivariable analysis a longer progression-free survival was associated with BRAF V600 (P = 0.093), female sex (P = 0.008), and M stage other than 1a (P = 0.024). When VLD occurred, there was a significant decrease of white blood cell (WBC) count (P = 0.05) and derived WBC-to-lymphocytes ratio (dWLR; P = 0.003). A lower monocyte count (P = 0.02) and dWLR (P = 0.01) were also reported in responder patients. CONCLUSIONS: Among VLD population, some features might help to identify patients with an effective response to immunotherapy, allowing clinicians to make more appropriate choices in terms of therapeutic options and duration.
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Inhibidores de Puntos de Control Inmunológico/efectos adversos , Ipilimumab/efectos adversos , Melanoma , Vitíligo , Anciano , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ipilimumab/uso terapéutico , Italia/epidemiología , Masculino , Melanoma/tratamiento farmacológico , Vitíligo/inducido químicamente , Vitíligo/diagnósticoRESUMEN
PURPOSE: Immunotherapy against immune checkpoints has significantly improved survival both in metastatic and adjuvant setting in several types of cancers. Thyroid dysfunction is the most common endocrine adverse event reported. Patients who are at risk of developing thyroid dysfunction remain to be defined. We aimed to identify predictive factors for the development of thyroid dysfunction during immunotherapy. METHODS: This is a retrospective study including a total of 68 patients who were treated with immune checkpoint inhibitors (ICIs) for metastatic or unresectable advanced cancers. The majority of patients were treated with anti-PD1 drugs in monotherapy or in combination with anti-CTLA4 inhibitors. Thyroid function and anti-thyroid antibodies, before starting immunotherapy and during treatment, were evaluated. Thyroid ultrasound was also performed in a subgroup of patients at the time of enrolment in the study. RESULTS: Eleven out of 68 patients (16.1%) developed immune-related overt thyroid dysfunction. By ROC curve analysis, we found that a serum TSH cut-off of 1.72 mUI/l, at baseline, had a good diagnostic accuracy in identifying patients without overt thyroid dysfunction (NPV = 100%, p = 0.0029). At multivariate analysis, both TSH and positive anti-thyroid antibodies (ATAbs) levels, before ICIs treatment, were independently associated with the development of overt thyroid dysfunction during immunotherapy (p = 0.0001 and p = 0.009, respectively). CONCLUSIONS: Pre-treatment serum TSH and ATAbs levels may help to identify patients at high risk for primary thyroid dysfunction. Our study suggests guidance for an appropriate timely screening and for a tailored management of thyroid dysfunctions in patients treated with ICIs.
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Inhibidores de Puntos de Control Inmunológico , Inmunoterapia/efectos adversos , Neoplasias , Enfermedades de la Tiroides , Autoanticuerpos/sangre , Antígeno CTLA-4/antagonistas & inhibidores , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/métodos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias/patología , Neoplasias/terapia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Estudios Retrospectivos , Medición de Riesgo/métodos , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/etiología , Enfermedades de la Tiroides/inmunología , Pruebas de Función de la Tiroides/métodos , Pruebas de Función de la Tiroides/estadística & datos numéricos , Tirotropina/sangreRESUMEN
Zearalenone, an oestogenic mycotoxin produced by Fusarium sp., occurs naturally in agricultural commodities. Economic losses and health concerns associated to mycotoxins has attracted research interest towards exploring novel approaches to detoxify mycotoxin-contaminated food and feed. The aim of the present work was to study the ability of 11 aflatoxin-degrading Bacillus strains to degrade ZEA. In addition, a qualitative assessment of protease, amylase and cellulase activity of the studied Bacillus strains was made. All strains were able to degrade 58-96.9% ZEA after 72 h. Toxicity towards Artemia salina was significantly reduced (P < 0.0001). Degradation extracts fluorescence decreased 50% indicating a probable cleavage of the lactone ring. Strains RC1A, RC3A and RC6A showed a remarkable enzymatic activity, showing potential to be used as feed additives.
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Aflatoxinas/metabolismo , Amilasas/metabolismo , Bacillus/metabolismo , Celulasas/metabolismo , Péptido Hidrolasas/metabolismo , Zearalenona/metabolismo , Agricultura , Inactivación MetabólicaRESUMEN
BACKGROUND: We conducted a retrospective exploratory analysis to evaluate the effects of baseline tumour immune infiltrate on disease-free survival (DFS) outcomes in patients with fully resected stage IIC-IIIC melanoma receiving adjuvant vemurafenib monotherapy or placebo in the BRIM8 study. PATIENTS AND METHODS: BRIM8 was a phase III, international, double-blind, randomised, placebo-controlled study. Eligible patients with BRAFV600 mutation-positive, completely resected melanoma were randomly assigned to oral vemurafenib (960 mg twice daily) or matching placebo for 52 weeks. The primary end point was DFS. The association of CD8+ T-cell infiltration and programmed death ligand 1 (PD-L1) expression with DFS, as measured by immunohistochemistry, was explored retrospectively. RESULTS: Four hundred ninety-eight patients were randomly assigned to receive adjuvant vemurafenib (n = 250) or placebo (n = 248); tumour samples were available for biomarker analysis for approximately 60% of patients. In the pooled biomarker population, placebo-treated patients with <1% CD8+ T cells in the tumour centre had shorter median DFS than those with ≥1% CD8+ T cells (7.7 versus 47.8 months). DFS benefit from vemurafenib versus placebo was greater in patients with <1% CD8+ T cells [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.34-0.92) than in patients with ≥1% CD8+ T cells (HR 0.77; 95% CI 0.48-1.22). Likewise, median DFS was shorter among placebo-treated patients with <5% versus ≥5% PD-L1+ immune cells (IC) in the tumour (7.2 versus 47.8 months). A greater DFS benefit with vemurafenib versus placebo was observed in patients with <5% PD-L1+IC (HR 0.36; 95% CI 0.24-0.56) than in patients with ≥5% PD-L1+IC (HR 0.99; 95% CI 0.58-1.69). CONCLUSIONS: The presence of CD8+ T cells and PD-L1+IC are favourable prognostic factors for DFS. Treatment with adjuvant vemurafenib may overcome the poor DFS prognosis associated with low CD8+ T-cell count or PD-L1 expression. CLINICALTRIALS. GOV IDENTIFIER: NCT01667419.
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Melanoma , Proteínas Proto-Oncogénicas B-raf , Supervivencia sin Enfermedad , Humanos , Melanoma/tratamiento farmacológico , Melanoma/genética , Mutación , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos , Vemurafenib/uso terapéuticoRESUMEN
Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel.The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.
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The multifaceted immunomodulatory activity of DNA hypomethylating agents improves immunogenicity and immune recognition of neoplastic cells; thus, we predicted they could be utilized to design new immunotherapeutic combinations in cancer. Testing this hypothesis, the antitumor efficacy of the DNA hypomethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) combined with the anti-CTLA-4 monoclonal antibody (mAb) 9H10 in syngeneic transplantable murine models was investigated. Murine mammary carcinoma TS/A or mesothelioma AB1 cells were injected in BALB/c, athymic nude, and SCID/Beige mice that were treated with 5-AZA-CdR, mAb 9H10, or their combination. Tumor volumes were captured at different time-points; molecular and immunohistochemical assays investigated changes in neoplastic and normal tissues. A significant antitumor effect of 5-AZA-CdR combined with mAb 9H10 was found: compared to controls, a 77% (p < 0.01), 54% (p < 0.01) and 33% (p = 0.2) decrease in TS/A tumor growth was induced by 5-AZA-CdR combined with mAb 9H10, 5-AZA-CdR or mAb 9H10, respectively. These antitumor activities were confirmed utilizing the AB1 model. 5-AZA-CdR-based regimens induced a promoter-demethylation-sustained tumor expression of cancer testis antigens. MHC class I expression was up-regulated by 5-AZA-CdR. Antitumor efficacy of 5-AZA-CdR in athymic nude and SCID/Beige mice was not increased by mAb 9H10. In BALB/c mice, combined treatment induced the highest tumor infiltration by CD3+ lymphocytes, which included both CD8+ and CD4+ T cells; no such infiltrates were observed in normal tissues. This significant immune-related antitumor activity of 5-AZA-CdR combined with CTLA-4 blockade, demonstrated in highly aggressive mouse tumor models, provides a strong scientific rationale to implement epigenetically-based immunotherapies in cancer patients.
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BACKGROUND: Ipilimumab improves the survival of metastatic melanoma patients. Despite documented, durable objective responses, a significant number of patients fails to benefit from treatment. The aim of this study was to identify an upfront marker for treatment benefit. METHODS: A total of 187 metastatic melanoma patients treated in three Italian Institutions with 3 mg kg(-1) ipilimumab, and 27 patients treated with 10 mg kg(-1) ipilimumab, were evaluated. Neutrophil-to-lymphocyte ratio (NLR) was calculated from pre-therapy full blood counts. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox models were applied, adjusting for confounders and other prognostic factors. RESULTS: In the training cohort of 69 patients treated at European Institute of Oncology, pre-therapy NLR was identified as the strongest and independent marker for treatment benefit in multivariate analyses. Patients with baseline NLR<5 had a significantly improved PFS (HR=0.38; 95% CI: 0.22-0.66; P=0.0006) and OS (HR=0.24; 95% CI: 0.13-0.46; P<0.0001) compared with those with a NLR⩾5. Associations of low NLR with improved survival were confirmed in three validation cohorts of patients. CONCLUSION: Our findings show that baseline NLR is strongly and independently associated with outcome of patients treated with ipilimumab, and may serve to identify patients most likely to benefit from this therapy.
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Anticuerpos Monoclonales/uso terapéutico , Linfocitos/patología , Melanoma/sangre , Melanoma/tratamiento farmacológico , Neutrófilos/patología , Adulto , Anciano , Biomarcadores de Tumor/sangre , Supervivencia sin Enfermedad , Femenino , Humanos , Ipilimumab , Masculino , Melanoma/patología , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Avian obligate brood parasites lay their eggs in nests of host species, which provide all parental care. Brood parasites may be host specialists, if they use one or a few host species, or host generalists, if they parasitize many hosts. Within the latter, strains of host-specific females might coexist. Although females preferentially parasitize one host, they may occasionally successfully parasitize the nest of another species. These host switching events allow the colonization of new hosts and the expansion of brood parasites into new areas. In this study, we analyse host switching in two parasitic cowbirds, the specialist screaming cowbird (Molothrus rufoaxillaris) and the generalist shiny cowbird (M. bonariensis), and compare the frequency of host switches between these species with different parasitism strategies. Contrary to expected, host switches did not occur more frequently in the generalist than in the specialist brood parasite. We also found that migration between hosts was asymmetrical in most cases and host switches towards one host were more recurrent than backwards, thus differing among hosts within the same species. This might depend on a combination of factors including the rate at which females lay eggs in nests of alternative hosts, fledging success of the chicks in this new host and their subsequent success in parasitizing it.
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Comportamiento de Nidificación/fisiología , Passeriformes/fisiología , Distribución Animal , Migración Animal , Animales , Conducta Competitiva , Flujo Génico , Marcadores Genéticos , Variación Genética , Haplotipos , Humanos , Datos de Secuencia Molecular , Oviposición , Passeriformes/genética , Especificidad de la EspecieRESUMEN
BACKGROUND: In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. PATIENTS AND METHODS: This analysis captured the 3-year outcome of MM patients who received ipilimumab combined with fotemustine as first- or second-line treatment. Median overall survival (OS), 3-year survival rates, immune-related (ir) progression-free survival (irPFS), brain PFS, and ir duration of response (irDOR) for the entire population and for patients with brain metastases were assessed. Clinical results were correlated with circulating CD3(+)CD4(+)ICOS(+)CD45RO(+) or CD45RA(+) T cells, neutrophil/lymphocyte (N/L) ratios, and tumorBRAF-V600 mutational status. RESULTS: Eighty-six MM patients, including 20 with asymptomatic brain metastases that had been pre-treated with radiotherapy in 7 subjects, were enrolled in the study. With a median follow-up of 39.9 months, median OS and 3-year survival rates were 12.9 months [95% confidence interval (CI) 7.1-18.7 months] and 28.5% for the whole study population, and 12.7 months (95% CI 2.7-22.7 months) and 27.8% for patients with brain metastases, respectively. Long-term ir adverse events consisting of G1 rush and pruritus occurred in 21% of patients. The absolute increase from baseline to week 12 in 'memory' but not in 'naïve' T cells identified patients with a better survival (P = 0.002). The N/L ratio correlated with a significantly better survival at early time points. BRAF status did not correlate with clinical outcome. CONCLUSIONS: Long-term analysis of the NIBIT-M1 trial continues to demonstrate efficacy of ipilimumab combined with fotemustine in MM patients. Fotemustine does not seem to impair the immunologic activity of ipilimumab. EUDRACT NUMBER: 2010-019356-50. CINICALTRIALSGOV: NCT01654692.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Biológica/mortalidad , Neoplasias Encefálicas/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Femenino , Estudios de Seguimiento , Humanos , Ipilimumab , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Compuestos de Nitrosourea/administración & dosificación , Compuestos Organofosforados/administración & dosificación , Pronóstico , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Tasa de SupervivenciaRESUMEN
Tyrant flycatchers (Aves: Tyrannidae) are endemic to the New World, and many species of this group are threatened or near-threatened at the global level. The aim of this study was to test the 18 microsatellite markers that have been published for other Tyrant flycatchers in the Strange-tailed Tyrant (Alectrurus risora) and the Sharp-tailed Tyrant (Culicivora caudacuta), two endemic species of southern South American grasslands that are classified as vulnerable. We also analyzed the usefulness of loci in relation to phylogenetic distance to the source species. Amplification success was high in both species (77 to 83%) and did not differ between the more closely and more distantly related species to the source species. Polymorphism success was also similar for both species, with 9 and 8 loci being polymorphic, respectively. An increased phylogenetic distance thus does not gradually lead to allelic or locus dropouts, implying that in Tyrant flycatchers, the published loci are useful independent of species relatedness.
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Especies en Peligro de Extinción , Evolución Molecular , Repeticiones de Microsatélite/genética , Passeriformes/genética , Animales , ADN Mitocondrial/genética , Passeriformes/clasificación , Filogenia , Polimorfismo GenéticoRESUMEN
The immune system balances effector responses with tolerance, to protect the host from pathogens while minimizing local damage to tissue. An altered control of immune homeostasis can lead to loss of tolerance to self antigens in autoimmunity, or promote unwanted tolerance to tumor growth. This review focuses on the dual activity of CD4(+) regulatory T cells (Tregs) in autoimmunity and cancer. Tregs play a key role in the mechanisms of immune tolerance and actively suppress pro-inflammatory responses, thus providing a beneficial action in autoimmunity and detrimental effects in cancer.
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Autoinmunidad , Neoplasias/inmunología , Linfocitos T Reguladores/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Factores de Transcripción Forkhead/metabolismo , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Linfocitos T Reguladores/metabolismoRESUMEN
PURPOSE: We evaluated the role of computed tomography (CT) for quantifying glenoid bone defects in patients with anterior glenohumeral instability and assisting in planning the most appropriate type of surgery. MATERIALS AND METHODS: From January to November 2006, 93 patients were studied by spiral CT with multiplanar reconstructions (MPR) for recurrent posttraumatic anteroinferior instability, chronic multidirectional instability and recurrent glenohumeral dislocation after surgical stabilisation. RESULTS: Quantitative CT enabled us to measure bone defects of the anteroinferior glenoid in terms of area (mm(2)) or surface percentage. Glenoid osseous defects were classified as small (<15%), medium (15%-20%), and large (>20%). CONCLUSIONS: CT quantification of glenoid bone loss is very accurate as well as rapid, simple and easily reproducible. CT therefore provides an important contribution to preoperative selection of patients, assisting in directing those with <20% bone loss towards arthroscopic capsular repair.
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Inestabilidad de la Articulación/diagnóstico por imagen , Escápula/diagnóstico por imagen , Escápula/patología , Luxación del Hombro/diagnóstico por imagen , Articulación del Hombro/diagnóstico por imagen , Tomografía Computarizada Espiral , Enfermedad Aguda , Adolescente , Adulto , Anciano , Artroscopía , Femenino , Humanos , Inestabilidad de la Articulación/patología , Inestabilidad de la Articulación/cirugía , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos , Recurrencia , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Luxación del Hombro/etiología , Luxación del Hombro/patología , Luxación del Hombro/cirugía , Articulación del Hombro/patología , Resultado del TratamientoRESUMEN
Primary hepatic epithelioid hemangioendothelioma (HEH) is a rare, low-grade malignant neoplasm of endothelial origin, with an unpredictable clinical course and prognosis. No standard therapeutic strategies are still available for HEH, due to the infrequency of the disease and to its variable natural history that limit the identification of the most effective treatment. In the absence of metastatic disease, surgical resection or liver transplantation represent the treatment of choice for HEH, while several antineoplastic agents have been proposed in the presence of metastatic nonresectable disesase. Herein, we describe the biological characterization and the clinical course of a primary HEH progressively responsive to treatment with intermediate doses of interferon-alpha (IFN)-alpha2a. Furthermore, based on the newly-identified expression of endoglin (CD105) on HEH, we discuss the clinical potential of novel anti-angiogenetic approaches to the disease.
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Inhibidores de la Angiogénesis/uso terapéutico , Hemangioendotelioma Epitelioide/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neovascularización Patológica/prevención & control , Antígenos CD/análisis , Antígenos CD34/análisis , Endoglina , Femenino , Hemangioendotelioma Epitelioide/irrigación sanguínea , Hemangioendotelioma Epitelioide/inmunología , Hemangioendotelioma Epitelioide/patología , Humanos , Inmunohistoquímica , Interferón alfa-2 , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Persona de Mediana Edad , Neovascularización Patológica/inmunología , Neovascularización Patológica/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Receptores de Superficie Celular/análisis , Proteínas Recombinantes , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
AIM: To retrospectively evaluate helical computed tomography (CT) findings in a series of consecutive patients with Budd-Chiari syndrome. METHODS: Patterns of enhancement observed at contrast-enhanced helical CT in 10 consecutive patients (six women, four men; aged 27-51 years) with either acute, subacute or chronic Budd-Chiari syndrome were retrospectively evaluated along with the status of the hepatic veins. All patients underwent triphasic helical CT (10 mm beam collimation, 7 mm rec. intervals, 120 kV, 200-250 mA, pitch = 1.0) performed at 20-25, 70-75 and 300 s after i.v. bolus (3 ml/s) injection of 150 ml iodinated non-ionic contrast media. RESULTS: Abnormal patterns of enhancement were identified in eight patients. In all patients with acute Budd-Chiari disease (3/3) abnormal arterial enhancement of the caudate lobe, the so-called "fan-shaped pattern" was observed, whereas visible venous thrombosis was only depicted in two. Conversely, a "patchy pattern" of enhancement was observed in five out of seven patients with either sub-acute (2) or chronic Budd-Chiari disease (5) along with a strip-like appearance or lack of visualization of hepatic veins. CONCLUSIONS: The "fan-shaped" pattern of enhancement represent a characteristic finding of acute Budd-Chiari disease, and it may help to suggest the correct diagnosis even in absence of visible venous thrombosis.
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Síndrome de Budd-Chiari/diagnóstico por imagen , Tomografía Computarizada Espiral , Enfermedad Aguda , Anciano , Enfermedad Crónica , Femenino , Venas Hepáticas/diagnóstico por imagen , Humanos , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada Espiral/métodos , Trombosis de la Vena/diagnóstico por imagenRESUMEN
A 58-year-old-man with unstable angina developed a violent retrosternal and interscapular pain during coronary angiography with no associated ECG abnormalities. The patient was immediately submitted to transesophageal echocardiography, which revealed an echo-free space behind the ascending aorta thought to be consistent with an aortic dissection. To confirm this finding the patient underwent contrast-enhanced helical CT, which ruled out a dissection but revealed a small hypoattenuating, ill-defined area within the lateral wall of the left ventricle, consistent with an acute myocardial infarction. The finding was first confirmed by bedside echocardiography and later validated by laboratory tests. Review of the left coronary angiogram showed the culprit lesion at the origin of a major acute marginal branch of the circumflex artery.
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Angina Inestable/complicaciones , Infarto del Miocardio/etiología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , RadiografíaRESUMEN
We describe a novel method for detecting micrometastasis in the blood stream of cancer patients based on RT-PCR amplification of tumor-associated carcinoembryonic antigen (CEA) mRNA. To increase sensitivity and specificity of RT-PCR, CEA transcript was selectively up-regulated in cancer cells by exposure of peripheral blood to non-toxic concentrations of staurosporine (ST). Thereafter, polyA(+) RNA was extracted from tumor cells captured by means of magnetic beads coated with a monoclonal antibody against a common human epithelial antigen. Finally, RNA was subjected to RT-PCR analysis of CEA transcript. Using this approach, we demonstrated an ST-mediated increase in CEA transcript in blood specimens collected from a patient with metastatic colon cancer before receiving treatment with 5-fluorouracil/leucovorin. After a few cycles of chemotherapy, CEA-positive tumor cells were no longer detected. Clinical follow-up of this patient indicated that treatment with chemotherapy induced a dramatic reduction in liver metastasis. Therefore, it can be hypothesized that lack of CEA transcript detection might be consistent with disappearance or at least marked reduction of circulating tumor cells.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno Carcinoembrionario/genética , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Células Neoplásicas Circulantes , ARN Mensajero/análisis , Adenocarcinoma/sangre , Adenocarcinoma/secundario , Antígeno Carcinoembrionario/metabolismo , Neoplasias del Colon/sangre , Neoplasias del Colon/patología , Cartilla de ADN/química , Femenino , Fluorouracilo/administración & dosificación , Humanos , Separación Inmunomagnética , Leucovorina/administración & dosificación , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/secundario , Persona de Mediana Edad , Pronóstico , ARN Neoplásico/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: Because leptin, the adipocyte-derived hormone, affects thymocyte survival, proliferation of naïve T lymphocytes and the production of proinflammatory cytokines, we aimed to investigate the role of this molecule in immunoreconstitution during highly active antiretroviral therapy (HAART). DESIGN: Prospective longitudinal cohort study. A series of 20 HIV+ children were studied. The subjects were grouped by their increase in serum leptin levels after HAART. METHODS: All participants were weight-stable, free of endocrine disorders and opportunistic infections and equally distributed for sex (males, n=10; females, n=10). Body mass index (BMI), serum lipids, leptin, CD4+ T cells and HIV-1 RNA were measured before initiation of HAART and after a 2-year follow-up. RESULTS: Serum leptin concentration positively correlated with CD4+ lymphocyte number before treatment. HAART significantly reduced viraemia and increased serum levels of lipids in all patients, whereas a significant increase in CD4+ cells and serum leptin was observed in the majority of patients. Notably, in children where HAART was not effective in increasing CD4+ lymphocyte counts, serum leptin did not increase. CONCLUSION: To our knowledge, these findings reveal for the first time a novel link among CD4+ T lymphocytes, serum leptin and highly active anteretroviral theraphy.