Evolución clínica y supervivencia de pacientes con melanomas de novo y melanomas asociados a nevo / Clinical evolution and survival of patients with de novo melanomas and nevus-associated melanomas

RESUMEN Introducción: El porcentaje de melanomas asociados histológicamente a nevos (MN(+)) varía del 20,6% al 53%. Distintos estudios demuestran que los MN(+) tienen igual o mejor pronóstico que aquellos melanomas que no se asocian a nevos, también llamados melanomas de novo (MN(-)). Objetivo: Comparar la evolución clínica y la supervivencia de MN(-) y MN(+) en el Hospital Privado Universitario de Córdoba, analizando el estudio de ganglio centinela, la supervivencia libre de enfermedad al año y a 5 años y la mortalidad específica por melanoma a 5 años. Materiales y Métodos :Se realizó un estudio retrospectivo, transversal. Se incluyeron pacientes con diagnóstico de melanoma cutáneo realizado por el Servicio de Anatomía Patológica del hospital o con revisión del taco de biopsia en el hospital, desde enero del año 2000 hasta diciembre del 2015. Resultados: De 554 casos de melanoma, se incluyeron 208 melanomas cutáneos, con un seguimiento promedio de 2,44 (0,66 - 5, 35) años. El 47,1% de melanomas fueron MN(+). Los MN(+) se relacionaron de manera estadísticamente significativa con el tipo extensivo superficial, localización en tronco posterior, regresión, menor Breslow y Clark 2. La supervivencia libre de enfermedad a 5 años fue mayor en MN(+) y la ausencia de asociación a nevo fue un factor de riesgo independiente. No se observaron diferencias en edad, sexo, diámetro tumoral, antecedentes de síndrome de nevo displásico, ulceración, mitosis, resultado del estudio de ganglio centinela, supervivencia libre de enfermedad al año, ni mortalidad por melanoma a 5 años.

ABSTRACT Introduction: The percentage of melanomas associated with nevus (NM(+)) ranges from 20,6% to 53%. Some studies suggested that MN+ have the same or even better prognosis than those melanomas that are not nevus-associated. The latter are also called melanomas de novo (MN(-)). Objective: To compare clinical evolution and survival of patients with MN(-) and MN(+) at the University Private Hospital of Cordoba (Argentina), by analyzing sentinel lymph node status, disease-free survival at 1 and 5 years and 5-year melanoma specific mortality. Methods: This is a retrospective, transversal study of patients who were diagnosed with cutaneous melanoma from 2000 until 2015. The biopsy specimen was analyzed or revised by the hospital´s Department of Pathology. Results: Of 554 melanoma cases, 208 cutaneous melanomas were included in the study. The mean follow up was 2,44 (0,66- 5,35) years. MN(+) represented the 47,1% of cases and were significantly correlated with superficial spreading subtype, posterior trunk localization, regression, lower Breslow and Clark 2. 5-year disease-free survival was longer in patients with MN(+) and the absence of associated nevus was an independent risk factor. There were no differences in age, gender, tumor diameter, history of atypical mole syndrome, ulceration, mitosis, sentinel lymph node status, 1-year disease-free survival or 5-year melanoma specific mortality.

Sarcoma de kaposi en pacientes vih: a proposito de dos casos / Kaposi´s sarcoma in hiv patients: regarding two case report

RESUMEN: El Sarcoma de Kaposi es unaneoplasia de origen vascular,asociado obligadamente al virus Herpes Humano tipo 8. Presenta manifestaciones cutáneas en primer lugar, mucosas, ganglionares y viscerales. Puede evolucionar de forma leve con lesiones cutáneas, hasta casos fulminantes con compromiso sistémico, en caso de no realizar tratamiento. Existen múltiples opciones terapéuticas, las cuales se definen según el compromiso de la enfermedad y la afectación del paciente por su patología de base.El diagnóstico se basa en la sospecha clínica y se confirma con una biopsia histopatológica. El sarcoma de Kaposi corresponde a la neoplasia más frecuente en los pacientes con VIHse encuentraprincipalmente en hombres homosexuales. En este artículo se presentan dos pacientes con VIH con diagnóstico de Sarcoma de Kaposi y se realiza una breve revisión de la bibliografía.

ABSTRACT: Kaposi´s sarcoma is a vascular origin neoplasm, obligatory associated with Human Herpes Virus 8. It presents cutaneous manifestations at a first place, mucous, ganglionic and viscerals. It may present a mild presentation with cutaneous manifestations, up to fulminant cases with systemicinvolvement,in case of not being treated. There are a number of therapeutic options, defined by the state of the illness and the involvement of the patient due to the primary pathology. The diagnosis is based on the clinical suspicion and it is confirmed by a histopathological biopsy. Kaposi´s sarcomais the most frequent neoplasm in patients with HIV, being more frequently in homosexual men. In this article two HIV patients with Kaposi´s sarcoma diagnosis are exposed and a brief revision of the literature is done.

Enfermedad de fabry / Fabry disease

RESUMEN La enfermedad de Fabry (EF) es un trastorno de almacenamiento lisosomal, hereditario, ligado al cromosoma X, causado por el déficit de la enzima alfa galactosidasa A. Presenta una gran variabilidad clínica por afección multisistémica de manera inespecífica. Por este motivo, el diagnóstico clínico de la enfermedad es difícil y suele retrasarse. Las manifestaciones cutáneas de esta patología, tienen un importante papel en el diagnóstico precoz de la enfermedad, ya que, permite la utilización de tratamiento de reemplazo enzimático oportuno, así como el consejo genético adecuado.

SUMMARY Fabry disease is a hereditary, lysosomal storage disorder linked to the X chromosome, caused by the deficiency of the enzyme alpha galactosidase A. It presents a great clinical variability due to multisystemic affection in an unspecific way. For this reason, the diagnosis of the disease is difficult and often delayed. The cutaneous manifestations of this pathology, have an important role in the early diagnosis of the disease, since it allows the use of opportune enzymatic replacement treatment, as well as the adequate genetic counseling.

Paniculitis por Candida en paciente trasplantado hepático / Candida Panniculitis in a liver trasnsplant patient

Los trasplantes de órganos sólidos, son tratamientos médico-quirúrgicos cada vez más habituales y suponen una importante mejora en la calidad de vida de los pacientes, con enfermedades graves. La inmunosupresión crónica, necesaria para evitar el rechazo del órgano trasplantado, aumenta el riesgo de complicaciones principalmente las de índole infecciosa. ¹ Dentro de las causas infecciosas, encontramos las de etiologías fúngicas siendo las más frecuentes, aquellas causadas por Candida albicans.

Solid organ transplants are increasingly common medical-surgical treatments and suppose a significant improvement in the quality of life of patients with serious diseases. Chronic immunosuppression, that is necessary to avoid rejection of the transplanted organ, increases the risk of complications mainly of infectious nature. Among the infectious causes we find those of fungal etiology being the most frequent those caused by Candida albicans.

Síndrome hipereosinofílico linfocítico: A propósito de dos casos / Lymphocytic hypereosinophilic syndrome: Two cases reported

El síndrome hipereosinofílico constituye un grupo de enfermedades, caracterizadas por sobreproducción de eosinófilos con el daño secundario de múltiples órganos, provocado por la infiltración eosinofílica y la liberación de mediadores de inflamación. Es infrecuente y su prevalencia desconocida. El principal factor pronóstico es el compromiso cardíaco.

The hypereosinofilic syndrome is a group of diseases characterized by overproduction of eosinophils with secondary multiple organ damage caused by the cells infiltration and release of mediators of inflammation. It is infrequent and its prevalence is unknown. The main prognostic factor is the cardiac involvement.

Angioleiomioma cavernoso cutáneo: Presentación de un caso / Cutaneous cavernous angioleiomyoma: A case report

El angioleiomioma es una neoplasia cutánea rara, benigna, que deriva de las células musculares lisas de los vasos sanguíneos. Se presenta habitualmente en los miembros inferiores de mujeres de edad mediana, como un tumor doloroso. El subtipo histológico cavernoso es poco frecuente. El tratamiento de elección es la extirpación quirúrgica de la lesión. Presentamos el caso de una paciente con un angioleiomioma cavernoso plantar izquierdo.(AU)

Angioleiomyoma is a rare, benign skin neoplasia derived from smooth muscle cells of blood vessels. It usually occurs in the lower limbs of middle-aged women as a painful tumor, palms and soles. The cavernous histological subtype is unusual. The treatment of choice is surgical removal of the lesion. We present a case of a patient with a left cavernous angioleiomyoma planting.(AU)

Angioleiomioma cavernoso cutáneo: Presentación de un caso / Cutaneous cavernous angioleiomyoma: A case report

El angioleiomioma es una neoplasia cutánea rara, benigna, que deriva de las células musculares lisas de los vasos sanguíneos. Se presenta habitualmente en los miembros inferiores de mujeres de edad mediana, como un tumor doloroso. El subtipo histológico cavernoso es poco frecuente. El tratamiento de elección es la extirpación quirúrgica de la lesión. Presentamos el caso de una paciente con un angioleiomioma cavernoso plantar izquierdo.

Angioleiomyoma is a rare, benign skin neoplasia derived from smooth muscle cells of blood vessels. It usually occurs in the lower limbs of middle-aged women as a painful tumor, palms and soles. The cavernous histological subtype is unusual. The treatment of choice is surgical removal of the lesion. We present a case of a patient with a left cavernous angioleiomyoma planting.

Focal nodular hyperplasia of the liver: an emerging complication of hematopoietic SCT in children.

Hepatic focal nodular hyperplasia (FNH) is a nonmalignant condition rarely affecting children previously treated for cancer, especially those who received hematopoietic SCT (HSCT). Some aspects of its pathogenesis still remain unclear and a strong association with specific risk factors has not yet been identified. We report here a single institution's case series of 17 patients who underwent HSCT and were diagnosed with FNH, analyzing retrospectively their clinical features and the radiological appearance of their hepatic lesions. We aimed to compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) and to explore the role of transient elastography (FibroScan) to evaluate the degree of hepatic fibrosis in FNH patients. Our analysis showed an association of FNH with age at transplant ⩽12 years (hazard ratio (HR) 9.10); chronic GVHD (HR 2.99); hormone-replacement therapy (HR 4.02) and abdominal radiotherapy (HR 4.37). MRI proved to be a more accurate diagnostic tool compared with US. Nine out of 12 patients who underwent FibroScan showed hepatic fibrosis. Our study points out that FNH is an emerging complication of HSCT, which requires a lifelong surveillance to follow its course in cancer patients.

Factores de riesgo para melanoma cutáneo: estudio de casos y controles en Córdoba, Argentina / Risk factors for cutaneous melanoma: case-control study in Córdoba, Argentina

Over the past years, considerable effort has been directed toward the identification of risk factors associated with the increasing incidence of cutaneous melanoma in white populations worldwide. Limited data are available from Argentine populations concerning risk factors for malignant melanoma. A case-control study was performed in Cordoba to estimate the risk factors for cutaneous malignant melanoma. The study group comprised 65 patients and 195 controls, matched by age and sex. The following risk factors were significant in the univariate analysis: European grandparents, blonde and brown hair, fair skin tone, light colored and brown eyes, presence of freckles and melanocytic nevi, severe sunburns before the age of 18 years, recreational sun exposure, family history of malignant melanoma. In the multivariate analysis, European grandparents (OR 2.27, IC95% 1.08 to 3.46), fair skin (OR 4.99, IC95% 2.72 to 7.28), severe sunburns before the age of 18 (OR 6.47, IC95% 5.29 to 7.65), and family history of malignant melanoma (OR 1525, IC95% 1467 to 1584), remain as independent risk factors for malignant melanoma. The results of the current study are similar to those obtained in other populations.

En los últimos años se han realizado considerables esfuerzos para identificar factores de riesgo asociados al incremento en la incidencia de melanoma maligno en la población blanca mundial. En Argentina los datos concernientes a factores de riesgo para melanoma maligno son limitados. Realizamos en el Hospital Privado de Córdoba un estudio de casos-controles con el objetivo de determinar factores de riesgo para melanoma maligno. El grupo de estudio fue de 65 pacientes con melanoma maligno y 195 controlespareados por sexo y edad. Los siguientes factores de riesgo fueron significativos en el análisis estadísticounivariado: abuelos nacidos en Italia o España y en otros países europeos, color de pelo castaño y claro, colorde piel claro, color de ojos marrón y claros, efélides, presencia de nevos melanocíticos, quemaduras solaresgraves antes de los 18 años de edad, exposición solar tanto laboral como recreativa y antecedente familiar demelanoma maligno, de éstos se mantienen como factores de riesgo independientes en el análisis multivariado abuelos nacidos en países europeos (OR 2.27, IC95% 1.08 a 3.46), piel clara (OR 4.99, IC95% 2.72 a 7.28) quemadura solar grave en más de 3 episodios antes de los 18 años (OR 6.47, IC95% 5.29 a 7.65) y antecedentes familiares de melanoma (OR 1525, IC95% 1467 a 1584). La mayoría de los datos que obtuvimos guardan semejanza con los descriptos en otras poblaciones.

Factores de riesgo para melanoma cutáneo: estudio de casos y controles en Córdoba, Argentina / Risk factors for cutaneous melanoma: case-control study in Córdoba, Argentina

Over the past years, considerable effort has been directed toward the identification of risk factors associated with the increasing incidence of cutaneous melanoma in white populations worldwide. Limited data are available from Argentine populations concerning risk factors for malignant melanoma. A case-control study was performed in Cordoba to estimate the risk factors for cutaneous malignant melanoma. The study group comprised 65 patients and 195 controls, matched by age and sex. The following risk factors were significant in the univariate analysis: European grandparents, blonde and brown hair, fair skin tone, light colored and brown eyes, presence of freckles and melanocytic nevi, severe sunburns before the age of 18 years, recreational sun exposure, family history of malignant melanoma. In the multivariate analysis, European grandparents (OR 2.27, IC95% 1.08 to 3.46), fair skin (OR 4.99, IC95% 2.72 to 7.28), severe sunburns before the age of 18 (OR 6.47, IC95% 5.29 to 7.65), and family history of malignant melanoma (OR 1525, IC95% 1467 to 1584), remain as independent risk factors for malignant melanoma. The results of the current study are similar to those obtained in other populations.

En los últimos años se han realizado considerables esfuerzos para identificar factores de riesgo asociados al incremento en la incidencia de melanoma maligno en la población blanca mundial. En Argentina los datos concernientes a factores de riesgo para melanoma maligno son limitados. Realizamos en el Hospital Privado de Córdoba un estudio de casos-controles con el objetivo de determinar factores de riesgo para melanoma maligno. El grupo de estudio fue de 65 pacientes con melanoma maligno y 195 controlespareados por sexo y edad. Los siguientes factores de riesgo fueron significativos en el análisis estadísticounivariado: abuelos nacidos en Italia o España y en otros países europeos, color de pelo castaño y claro, colorde piel claro, color de ojos marrón y claros, efélides, presencia de nevos melanocíticos, quemaduras solaresgraves antes de los 18 años de edad, exposición solar tanto laboral como recreativa y antecedente familiar demelanoma maligno, de éstos se mantienen como factores de riesgo independientes en el análisis multivariado abuelos nacidos en países europeos (OR 2.27, IC95% 1.08 a 3.46), piel clara (OR 4.99, IC95% 2.72 a 7.28) quemadura solar grave en más de 3 episodios antes de los 18 años (OR 6.47, IC95% 5.29 a 7.65) y antecedentes familiares de melanoma (OR 1525, IC95% 1467 a 1584). La mayoría de los datos que obtuvimos guardan semejanza con los descriptos en otras poblaciones.(AU)

[Transcranial Doppler imaging: state of the art]. / Echo-Doppler transcrânien: Mise au point.

Initially introduced in the early 1980's, transcranial Doppler followed by transcranial Doppler sonography were used in neurosurgical units for management and follow-up of intracranial vasospasm in patients with subarachnoid hemorrhage. This imaging technique, more sensitive and less invasive than catheter angiography, also proved to be of value for diagnosis of intracranial atherosclerosis, management of patients with head trauma, and evaluation of collateral flow through the circle of Willis. Doppler US would also allow prediction of the risk of symptomatic embolic events through monitoring of HITS. Evaluation of the middle cerebral arteries during carotid occlusion testing is useful for evaluating the need for particular revascularization techniques. Finally, Doppler imaging is useful to assess patients with possible brain death. A recent advance in Doppler imaging is the ability to provide a three-dimensional projection (3D Doppler) of the intracranial arteries enabling improved detection and evaluation of stenoses involving the circle of Willis and improved characterization of intracranial aneurysms. These new applications benefit from the use of US contrast agents and harmonic US imaging.

Osteoarthritic lesions: involvement of three different collagenases.

OBJECTIVE: To assess the presence of fibroblast collagenase (MMP-1), neutrophil collagenase (MMP-8), and collagenase 3 (MMP-13) in osteoarthritic (OA) cartilage, with particular emphasis on areas of macroscopic cartilage erosion. METHODS: Messenger RNA (mRNA) levels were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization, and Northern blot analysis. RESULTS: MMP-1 and MMP-13 were expressed at higher levels by OA chondrocytes than by normal chondrocytes. In addition, mRNA for MMP-8 was present in OA cartilage but not normal cartilage by PCR and Northern blot analyses. Chondrocytes from areas surrounding the OA lesion expressed greater quantities of MMP-1 and MMP-13 compared with normal chondrocytes, suggesting local modulation by mechanical and inflammatory factors. Tumor necrosis factor alpha stimulated the expression of all 3 collagenases. Retinoic acid, an agent which induces autodigestion of cartilage in vitro, stimulated only the expression of MMP-13. CONCLUSION: These findings suggest a key role of MMP-13 and MMP-8, as well as MMP-1 in osteoarthritis.

Buflomedil interference with the monoclonal EMIT d.a.u. amphetamine/methamphetamine immunoassay.

The interference of buflomedil with the monoclonal and polyclonal EMIT d.a.u. amphetamine immunoassays was investigated. Urine samples collected from 20 patients taking 600 mg of buflomedil daily gave false positive results with the monoclonal EMIT d.a.u. assay, as did urine specimens collected 2 hours after the first oral dose of buflomedil. Conversely, no false positive results occurred with the polyclonal EMIT d.a.u. amphetamine assay. Urine samples with buflomedil added at concentrations greater than 100 mg/l gave false positive results with the monoclonal immunoassay. Buflomedil concentrations found in the patient urines (56-400 mg/l) failed to correlate to EMIT assay responses: this result suggests that one or more buflomedil metabolites, besides the unchanged drug, probably interfere in the monoclonal EMIT d.a.u. assay.

[Results of ultrasonographic and cytologic follow-up of 311 initially non-suspicious thyroid nodules]. / Résultats de la surveillance échographique et cytologique de 311 nodules thyroïdiens initialement non suspects.

The follow-up of initially non suspect thyroid nodules after fine needle biopsy is not completely worked out. Since 1985, we have entered upon a prospective study concerning the followup of thyroid nodules supposed to be benign after initial evaluation. What are the nature and the frequency of means to be used for their follow-up? Three hundred and eleven nodules are followed up on a mean duration of 2.44 years. The follow-up of 65 of them is 4 years or more. The follow-up of 120 others is 3 to 4 years; 197 nodules are followed up during 2 to 3 years. A physical examination, an ultrasonography completed with a fine needle biopsy or an ultrasonically guided fine needle biopsy are worked out every year. Twenty-three per cent of initial biopsies are non significant and 90% of them are ultrasonically guided biopsies. At the end of the study, the repeating biopsies reduce to 6% the non significant biopsies ratio. Four histological thyroid cancers are detected in three female patients 1 year, 2 years and 5 years after the initial evaluation. Ultrasound alterations of nodules are observed in case of very suspect biopsies. Ninety-six per cent of the followed up thyroid nodules remain not cytologically suspect. These findings allow us to propose the following guidelines for the assessment of a non suspect thyroid nodule: half-yearly or yearly physical examination, yearly or biennial ultrasonography, repeat biopsy after 2 or 3 years when clinical or ultrasound suspect modification is wanting.

Role of the conserved histidine and aspartic acid residues in activity and stabilization of human gelatinase B: an example of matrix metalloproteinases.

Gelatinase B (MMP-9), a member of the matrix metalloproteinase family, is a zinc- and calcium-dependent endopeptidase that is known to play a role in tumor cell invasion and in destruction of cartilage in arthritis. It contains a conserved sequence. 400His-(X)3-His-(X)28-Asp-Asp-(X)2-436Gly, the function of which is under investigation. The conserved Asp-432 and Asp-433 residues were individually replaced with Gly; these substitutions reduced the gelatinolytic activity of the enzyme to 23% and 0%, respectively. Replacing Asp-433 with Glu, however, decreased the gelatinolytic activity of the enzyme by 93% and proteolytic activity of the enzyme for the Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 substrate by 79%. The wild-type and D432G and D433E, mutant enzymes had similar Km values for the synthetic substrate and similar Ki values for the competitive inhibitor, GM6001. The kcat/Km values for D432G and D433E mutant enzymes, however, were reduced by a factor of approximately 4 and their KaCa values were increased by four- and sixfold, respectively. The significance of His-400 in the activity of the enzyme was assessed by replacing this residue with Ala and Phe. Both H400A and H400F mutants were inactive toward gelatin substrate. These data demonstrate that Asp-432, Asp-433, and His-400 residues are important for the activity of gelatinase B. His-400 may act as a zinc-binding ligand similar to the His-197 in interstitial collagenase (MMP-7) and Asp-432 and Asp-433 residues are probably involved in stabilization of the active site of the enzyme. The His-400 and Asp-433 residues are conserved in all members of the MMP family. Therefore, our results are relevant to this group as a whole.

[Nodular or pseudo-nodular Hashimoto thyroiditis. Value of cytologic examination]. / Thyroïdites de hashimoto à aspect nodulaire ou pseudo-nodulaire. Intérêt de l'examen cytologique.

OBJECTIVES: Nodular or pseudo-nodular aspects of Hashimoto's thyroiditis raise the problem of the association with a differentiated carcinoma or a non Hodgkin's lymphoma. METHODS: We looked for patients needing surgery in 165 cases of Hashimoto's thyroiditis. For this purpose, we used fine needle aspiration cytology. RESULTS: We found a differentiated carcinoma in 4% of cases and a non Hodgkin's lymphoma in 1% of cases. CONCLUSION: In nodular or pseudo-nodular aspects of Hashimoto's thyroiditis, fine needle aspiration cytology is helpful for the nodule diagnosis and for the selection of suspicious nodules only to be referred to surgery.

[The transplanted kidney. Role of imaging in early non-functioning grafts]. / Rein transplanté. Place de l'imagerie dans les non-fonctions précoces.

Renal failure following transplantation can be classified in two groups: initial non function characterized by the absence of renal function after transplantation and delayed secondary non function after an initial improvement. In the first group, the most frequent etiology is an acute tubular necrosis (30 to 50% of the cases) which usually heals within three weeks. Arterial thrombosis are rare but of very bad prognosis. In the second group, the most frequent cases are acute rejection, urological complications, renal artery stenosis, urinary infections and cyclosporine, intoxication. Diagnostic imaging, and especially the color Doppler flow, is very effective in obtaining diagnosis. Vascular or urological complications are to be confirmed by contrasted opacifications. In the absence of vascular or urological obstruction renal failure must be related to a renal parenchymal disease. This may be acute tubular necrosis, a rejection, a pyelonephritis or a medicinal intoxication depending on clinical symptoms, the time of their apparition and the results of biological examinations.