RESUMEN
Introducción: los prolactinomas son los adenomas hipofisarios funcionantes más frecuentes y la primera opción de tratamiento es la farmacológica en la mayoría de los casos. La cirugía está indicada en pacientes con resistencia o con intolerancia a los Agonistas Dopaminérgicos (AD). Objetivos: evaluar las características clínicas, bioquímicas y por imágenes de un grupo de pacientes con prolactinomas que requirieron Cirugía Endoscópica Endonasal (CEE) y analizar los resultados quirúrgicos. Material y métodos: se analizaron en forma retrospectiva las historias clínicas de 17 pacientes (8 mujeres /9 varones) con diagnóstico de prolactinoma pertenecientes a dos hospitales de la ciudad de Buenos Aires, los cuales fueron intervenidos quirúrgicamente en el periodo comprendido entre enero de 2011 y junio de 2021. Se analizaron las indicaciones de la cirugía y los resultados quirúrgicos obtenidos, y se realizó una revisión de la literatura referente al tema. Resultados: Las indicaciones para la cirugía en los 17 pacientes fueron: 8 resistencia a los AD, 2 intolerancia a los AD, 2 apoplejía tumoral, 2 fístula de líquido cefalorraquídeo (LCR), 1 adenoma quístico, 1 compromiso visual severo y 1 macroadenoma por sospecha de adenoma no funcionante (ANF). Según el tamaño tumoral, se clasificaron en 16 macroadenomas (Ma), 5 de ellos > 4 cm o gigantes (G), y sólo una paciente con microadenoma (Mi) e intolerancia a los AD. Se logró la resección total en 8 pacientes, subtotal en 5 y parcial en 4. Se obtuvo la remisión bioquímica en 7 casos (41,2%) con cirugía (1 Mi /5 Ma/1 G) y los 10 restantes (6 Ma/4 G) requirieron terapia farmacológica y/o radioterapia (RT) adyuvante, de los cuales 5 se encuentran con enfermedad activa. Publicaciones recientes avalan el resurgimiento del tratamiento quirúrgico para este subtipo de adenomas, sobre todo en microadenomas, debido principalmente al perfeccionamiento de la técnica quirúrgica, que permitió obtener mejores resultados postoperatorios en relación a la remisión bioquímica y menor tasa de complicaciones. Conclusión.La CEE permite una alta tasa de curación en microprolactinomas y macroprolactinomas no invasores debiendo ser considerada como una opción viable y concreta durante la evaluación multidisciplinaria de estos pacientes(AU)
Background: prolactinomas are the most frequent functioning pituitary adenomas and the first treatment option is pharmacological in most of them. Surgery is indicated in patients with resistance or intolerance to Dopaminergic Agonists (DA). Objectives: to evaluate the clinical, biochemical and imaging characteristics of a group of patients with prolactinomas who required Endonasal Endoscopic Surgery (EES) and to analyze the surgical results. Methods: the medical records of 17 patients (8 women / 9 men) diagnosed with prolactinoma belonging to two hospitals in the city of Buenos Aires, who underwent surgery in the period from January 2011 and June 2021. The indications for surgery and the surgical results obtained were analyzed, and a review of the literature on the subject was carried out. Results: The indications for surgery in the 17 patients were: 8 DA resistance, 2 DA intolerance, 2 tumor apoplexy, 2 cerebrospinal fluid (CSF) fistula, 1 cystic adenoma, 1 severe visual impairment, and 1 macroadenoma due to suspected non-functional adenoma (NFA). According to tumor size, they were classified into 16 macroadenomas (Ma), 5 of them > 4 cm or giant (G), and only one patient with microadenoma (Mi) and intolerance to AD. Total resection was obtained in 8, subtotal in 5 and partial in 4 patients. Biochemical remission was obtained in 7 cases (41.2%) with surgery (1 Mi/5 Ma/1Gi) and the remaining 10 (6 Ma/4 Gi) required drug therapy and/or adjuvant radiotherapy (RT), 5 of whom are with active disease. Recent publications support the resurgence of surgical treatment for this subtype of adenomas, especially in microadenomas, mainly due to the improvement of surgical techniques, which showed better postoperative results in relation to biochemical remission and a lower rate of complications. Conclusion: EESallows a high cure rate in microprolactinomas and in non-invasive macroprolactinomas, and should be considered as a viable and concrete therapeutic option during the multidisciplinary evaluation of these patients(AU)
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Endoscopía , Cirugía General , Prolactinoma , Adenoma , Agonistas de DopaminaRESUMEN
BACKGROUND: The success of HER2-positive (HER2+) breast cancer treatment with trastuzumab, an antibody that targets HER2, relies on immune response. We demonstrated that TNFα induces mucin 4 (MUC4) expression, which shields the trastuzumab epitope on the HER2 molecule decreasing its therapeutic effect. Here, we used mouse models and samples from HER2+ breast cancer patients to unravel MUC4 participation in hindering trastuzumab effect by fostering immune evasion. METHODS: We used a dominant negative TNFα inhibitor (DN) selective for soluble TNFα (sTNFα) together with trastuzumab. Preclinical experiments were performed using two models of conditionally MUC4-silenced tumors to characterize the immune cell infiltration. A cohort of 91 patients treated with trastuzumab was used to correlate tumor MUC4 with tumor-infiltrating lymphocytes. RESULTS: In mice bearing de novo trastuzumab-resistant HER2+ breast tumors, neutralizing sTNFα with DN induced MUC4 downregulation. Using the conditionally MUC4-silenced tumor models, the antitumor effect of trastuzumab was reinstated and the addition of TNFα-blocking agents did not further decrease tumor burden. DN administration with trastuzumab modifies the immunosuppressive tumor milieu through M1-like phenotype macrophage polarization and NK cells degranulation. Depletion experiments revealed a cross-talk between macrophages and NK cells necessary for trastuzumab antitumor effect. In addition, tumor cells treated with DN are more susceptible to trastuzumab-dependent cellular phagocytosis. Finally, MUC4 expression in HER2+ breast cancer is associated with immune desert tumors. CONCLUSIONS: These findings provide rationale to pursue sTNFα blockade combined with trastuzumab or trastuzumab drug conjugates for MUC4+ and HER2+ breast cancer patients to overcome trastuzumab resistance.
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Mucina 4 , Neoplasias , Ratones , Animales , Trastuzumab/farmacología , Trastuzumab/uso terapéutico , Regulación hacia Abajo , Mucina 4/genética , Mucina 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Receptor ErbB-2 , Línea Celular Tumoral , Terapia de Inmunosupresión , Neoplasias/tratamiento farmacológicoRESUMEN
PURPOSE: Non-invasive encapsulated follicular variant of papillary thyroid cancer was reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). These neoplasms have an extremely low malignant potential. The aim of this study was (1) to assess the prevalence of NIFTP in patients with papillary thyroid carcinoma, (2) to evaluate their outcomes, and (3) to determine their molecular profile. METHODS: Multicenter, descriptive, retrospective study. Patients with papillary thyroid cancer diagnosed from January 2006 to December 2016 from 11 referral centers were included. Diagnosis of NIFTP was based on criteria described by Nikiforov et al. in 2018. At least two pathologists agreed on the diagnosis. Two thousand six hundred and seventy-seven papillary thyroid cancer patients were included; 456 (17%) of them were follicular variant papillary thyroid cancer, and 30 (1.12%) fulfilled diagnostic criteria for NIFTP. RESULTS: Each of the 30 included patients underwent a total thyroidectomy, and 50% were treated with radioiodine (median dose 100 mCi). After a median follow-up of 37 months, 84% of patients had an excellent response, 3% had an indeterminate response and data was missing in the remaining 13%. No metastatic lymph nodes, distant metastases or recurrences were found. RAS mutations were detected in 4 patients (13%). CONCLUSION: The prevalence of NIFTP in our series is amongst the lowest reported. Excellent outcomes of patients underscore their low malignant potential. Molecular findings differ from other series, probably related to environmental or ethnic features of our population and the meticulous criteria for diagnosing NIFTP.
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Adenocarcinoma Folicular , Neoplasias de la Tiroides , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/epidemiología , Adenocarcinoma Folicular/genética , Argentina/epidemiología , Humanos , Radioisótopos de Yodo , Estudios Retrospectivos , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/epidemiología , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/genéticaRESUMEN
Triple negative breast cancer (TNBC) refers to tumors that do not express clinically significant levels of estrogen and progesterone receptors, and lack membrane overexpression or gene amplification of ErbB-2/HER2, a receptor tyrosine kinase. Transcriptome and proteome heterogeneity of TNBC poses a major challenge to precision medicine. Clinical biomarkers and targeted therapies for this disease remain elusive, so chemotherapy has been the standard of care for early and metastatic TNBC. Our present findings placed ErbB-2 in an unanticipated scenario: the nucleus of TNBC (NErbB-2). Our study on ErbB-2 alternative splicing events, using a PCR-sequencing approach combined with an RNA interference strategy, revealed that TNBC cells express either the canonical (wild-type) ErbB-2, encoded by transcript variant 1, or the non-canonical ErbB-2 isoform c, encoded by alternative variant 3 (RefSeq), or both. These ErbB-2 isoforms function in the nucleus as transcription factors. Evicting both from the nucleus or silencing isoform c only, blocks TN cell and tumor growth. This reveals not only NErbB-2 canonical and alternative isoforms role as targets of therapy in TNBC, but also isoform c dominant oncogenic potential. Furthermore, we validated our findings in the clinic and observed that NErbB-2 correlates with poor prognosis in primary TN tumors, disclosing NErbB-2 as a novel biomarker for TNBC. Our discoveries challenge the present scenario of drug development for personalized BC medicine that focuses on wild-type RefSeq proteins, which conserve the canonical domains and are located in their classical cellular compartments.
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Receptor ErbB-2/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Línea Celular Tumoral , Núcleo Celular/enzimología , Núcleo Celular/metabolismo , Proliferación Celular/fisiología , Femenino , Humanos , Proteína Quinasa 7 Activada por Mitógenos/biosíntesis , Proteína Quinasa 7 Activada por Mitógenos/genética , Adhesión en Parafina , Isoformas de Proteínas , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/genética , Neoplasias de la Mama Triple Negativas/enzimología , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
The hormone receptor-positive (estrogen and/or progesterone receptor (PR)-positive) and HER2-negative breast cancer (BC) subtype is a biologically heterogeneous entity that includes luminal A-like (LumA-like) and luminal B-like (LumB-like) subtypes. Decreased PR levels is a distinctive biological feature of LumB-like tumors. These tumors also show reduced sensitivity to endocrine therapies and poorer prognosis than LumA-like tumors. Identification of biomarkers to accurately predict disease relapse in these subtypes is crucial in order to select effective therapies. We identified the tumor suppressor PDCD4 (programmed cell death 4), located in the nucleus (NPDCD4), as an independent prognostic factor of good clinical outcome in LumA-like and LumB-like subtypes. NPDCD4-positive LumB-like tumors presented overall and disease-free survival rates comparable to those of NPDCD4-positive LumA-like tumors, indicating that NPDCD4 improves the outcome of LumB-like patients. In contrast, NPDCD4 loss increased the risk of disease recurrence and death in LumB-like compared with LumA-like tumors. This, along with our results showing that LumB-like tumors present lower NPDCD4 positivity than LumA-like tumors, suggests that NPDCD4 loss contributes to endocrine therapy resistance in LumB-like BCs. We also revealed that PR induces PDCD4 transcription in LumB-like BC, providing a mechanistic explanation to the low PDCD4 levels in LumB-like BCs lacking PR. Finally, PDCD4 silencing enhanced BC cell survival in a patient-derived explant model of LumB-like disease. Our discoveries highlight NPDCD4 as a novel biomarker in LumA- and LumB-like subtypes, which could be included in the panel of immunohistochemical markers used in the clinic to accurately predict the prognosis of LumB-like tumors.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Neoplasias de la Mama/genética , Proteínas de Unión al ARN/metabolismo , Neoplasias de la Mama/patología , Femenino , Humanos , PronósticoRESUMEN
Introducción: Las infecciones transmisibles sexualmente (ITS) son motivo de consulta frecuente, encontrándose Chlamydia trachomatis (CT) entre las prevalentes. Este germen provoca proctitis de diversa gravedad según el biovar involucrado. Los casos más floridos suelen ser ocasionados por el biovar LGV, responsable de la entidad linfogranuloma venéreo. Se desconocen la prevalencia de CT como causa de proctitis en Argentina y los biovares implicados. Con el objetivo de estudiar estas variables, se diseñó un protocolo para detectar y genotipificar CT en pacientes con proctitis infecciosa. Pacientes y métodos: Se incluyeron pacientes mayores de 18 años con cuadro de proctitis infecciosa atendidos en un centro público y otro privado. Se excluyeron pacientes con enfermedad inflamatoria intestinal y radioterapia pelviana. El estudio fue aprobado por un Comité de Ética y los pacientes firmaron un consentimiento informado. En las muestras de hisopado anal se realizó detección y tipificación molecular de CT. Resultados: Entre 31de agosto de 2017 y 31 de mayo de 2018, se incluyeron 56 pacientes (1 mujer, 53 hombres, 2 mujeres trans), 79% HIV+. En 29 casos (52%) se detectó CT. Todos eran hombres que tienen sexo con hombres (HSH) y refirieron practicar sexo anal u oral receptivo no protegido. La mediana de edad de este subgrupo fue de 31 años; 83% HIV+ en tratamiento antirretroviral y mediana de CD4 637 cel/mm3. La coinfección con otras ITS fue del 41% (siendo las más frecuentes HPV, gonococia y sífilis). Los motivos de consulta más frecuentes fueron proctorragia, pujo y tenesmo, proctalgia y secreción. Las manifestaciones clínicas fueron variadas: proctitis, úlcera perianal, tumor endoanal/rectal y absceso/fístula. El 86% de las proctitis correspondió al biovar LGV, siendo 62% moderadas a graves. La mediana de tiempo de evolución hasta el diagnóstico fue 21 días. Los casos más prolongados correspondieron a cuadros clínicos y endoscópicos más graves. La duración del tratamiento se adecuó al biovar involucrado. Todos los pacientes respondieron favorablemente; sin embargo, las dos fístulas perianales requirieron resolución quirúrgica. Conclusiones: Proctitis, úlceras y fístulas son manifestaciones inespecíficas; el hallazgo clínico y endoscópico per se no son suficientes para definir la etiología; sólo una anamnesis minuciosa permite presumir una ITS como agente causal. La tipificación logra definir el biovar, dato fundamental para adecuar el tratamiento, cortar la cadena de transmisión y contar con datos epidemiológicos a nivel local. Como resultado de esta investigación, el Ministerio de Salud de Nación proyectó la emisión de una alerta sobre la presencia de LGV en nuestro medio. Tipo de estudio: Observacional, transversal, analítico, multicéntrico.
Introduction: Sexually transmitted infections (STI) are a frequent reason for consultation, being Chlamydia trachomatis (CT) among the most prevalent ones. It causes proctitis of varying severity depending on the biovar involved. The most severe cases are usually caused by the LGV biovar, responsible for the entity called lymphogranuloma venereum. The prevalence of CT as a cause of proctitis in Argentina and the biovars involved are unknown. In order to study these variables, a protocol was designed to detect and genotype CT in patients with infectious proctitis. Patients and methods: Patients over 18 years old with infectious proctitis were attended in a public and private center. Patients with inflammatory bowel disease and pelvic radiation therapy were excluded. The study was approved by an Ethics Committee and the patients signed an informed consent. The detection and molecular typing of CT was performed in anal swab samples. Results: Between 31-08-2017 and 31-05-2018, 56 patients were included (1 woman, 53 men, 2 trans women), 79% HIV +. In 29 cases (52%) CT was detected. All were MSM and reported to practice unprotected receptive oral or anal sex. The median age of this subgroup was 31 years; 83% HIV + on antiretroviral treatment and median CD4 637 cel / mm3. The coinfection with other STIs was present 41% (the most frequent were HPV, gonococcal and syphilis). The most frequent symptoms were bleeding, tenesmus, proctalgia and secretion. The clinical manifestations were varied: proctitis, perianal ulcer, endoanal / rectal tumor and abscess / anal fistula. 86% of the proctitis corresponded to the LGV biovar, being 62% moderate to severe. The median time of evolution until the diagnosis was 21 days. The most prolonged cases corresponded to more severe clinical and endoscopic symptoms. The duration of the treatment was adapted to the biovar involved. All patients responded favorably; however, the two perianal fistulas required surgical resolution. Conclusions: Proctitis, ulcers and fistulas are nonspecific manifestations; the clinical and endoscopic findings per se are not sufficient to define the etiology; only a meticulous anamnesis allows us to presume an STI as a causative agent. The typification allows to define the biovar, a fundamental data to adapt the treatment, stop chain of transmission and provides local epidemiological data. As a result of this investigation, the Ministry of Health of the Argentina issued an alert about the presence of LGV in our country. Type of study: Observational, cross-sectional, analytical, multicenter study.
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Humanos , Masculino , Femenino , Adulto , Adulto Joven , Proctitis/etiología , Proctitis/epidemiología , Infecciones por Chlamydia , Chlamydia trachomatis/patogenicidad , Enfermedades del Recto/etiología , Enfermedades del Recto/epidemiología , Linfogranuloma Venéreo/etiología , Infecciones por VIH/complicaciones , Prevalencia , Homosexualidad MasculinaRESUMEN
Paracoccidioides brasiliensis is the predominant dimorphic fungal disease in Latin America. Males between 29 to 40 years of age are most often affected. Inhalation of the infecting particle produces a localized alveolitis. The organisms then may disseminate to the skin, mucous membranes, lymph nodes, adrenal glands, liver, spleen, bones, central nervous system and digestive tract, giving a multisystemic affectation, mainly in immunocompromised hosts. A male 34 years old with a history of immunocompromised VIH +, was studied. The characteristics in authopsy are described, with previous diagnosis of diseminated. Paracoccidioides brasiliensis, with intraalveolar hemorrhage, pleuritis and pericarditis. Deep systemic micosis and opportunistic are pathologies that present with increased frequency in recent years, mainly by the rise of the VIH+ infected population. Despite this circumstance, the coexistence of Paracoccidioide infection and VIH+ is scarce in the literature, and for that reason, we present this case of autopsy.
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Humanos , Masculino , Adulto , Paracoccidioidomicosis/diagnóstico , Pericarditis/diagnóstico , Pleuresia/diagnóstico , Autopsia , VIH/inmunología , Huésped Inmunocomprometido , HemorragiaRESUMEN
During history, amylidosis was observed associated to a great variety of inflammatory diseases, and due to this, appeared the term "secondary amyloidosis". The forms of sudden presentation without any apparent cause are classified as "primary amyloidosis", and also the localized amyloidosis was characterized, the same as the heredity variant. At present, three main grops are recognized as systemic amyloidosis: amyloidosis of light chains, the amyloidosis associated to the seric protein A, and the hereditary form. Systemic amyloidosis can involve practically any organ system, being the most commonly affected the heart and the kidney, which therefore determine the clinical evolution and the prognosis of the patient. The aim of this report, was to present a case of autopsy of systemic amyloidosis with involvement of the Central Nervous System, considering besides, the great extension of the disease in our patient
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Humanos , Femenino , Persona de Mediana Edad , Autopsia , Inmunohistoquímica , Escala de Coma de Glasgow , Placa Amiloide/fisiopatología , Disección , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Sistema Nervioso Central/patologíaRESUMEN
This study examines a description of pituitary tumors considering an anatomopathological casuistic. The study of the tumors of the Central Nervous System (CNS) include the pituitary gland, located in the sella turcica. The pathology of the sellar region is represented by the adenomas, tumors of slow development with or without endocrine secretion, that usually involve the population of young adults. The aim of this report, was to describe the casuistic of the " J. Fernandez Hospital" between the years 2000 through 2017. A retrospective review was performed and 234 samples of the sellar region were processed. Mean age was 42 years with a range of 17 to 77 years. Sex distribution was 57% women and 43 % men. Of these, 77% of the cases resulted adenomas. The conclusions obtained in the study are detailed.
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Humanos , Adulto , Persona de Mediana Edad , Anciano , Adenohipófisis/patología , Neoplasias Hipofisarias/patología , Silla Turca/patología , Sistema Nervioso Central/patología , Neoplasia Endocrina Múltiple Tipo 1/genética , DiagnósticoRESUMEN
Renal biopsy is a key procedure for the evaluation and management of the renal diseases, in order to establish a certainty diagnosis, to perform an adequate treatment and to determine the prognosis, while it results in a fundamental tool, but not all the medical centers have the necessary requeriments to carry them succesfully so that it can achieve the maximum benefit, lessen the posible complications, since as it is an invasive technique, always exists a certain risk inherent to the procedure, being the technique of choice the percutaneous renal biopsy guided by ultrasound. The aim of this report, is to know the incidence of the reanl pathology, in kidney biopsies in our Hospita, between July 2008 through July 2017, by mean of a descriptive and retrospective study. Two-thousands and eightsi-six reanl biopsies were analyzed in that period, and we analyzed the frequency of the disease diagnosed, the origin of the samples and thir quality, the age range of the population studied, as well as the complications of the method employed
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Humanos , Patología Clínica , Procedimientos Quirúrgicos Mínimamente Invasivos , Biopsia Guiada por Imagen/métodos , Riñón/patología , Enfermedades Renales/diagnósticoRESUMEN
Introducción: El cáncer anal, asociado a la infección con virus de papiloma humano de alto riesgo (HPV-AR), es muy frecuente en hombres que tienen sexo con hombres (HSH) HIV+. Objetivo: Evaluar frecuencia de infección por HPV-AR, genotipos y lesiones asociadas, y factores asociados.Materiales y métodos: Estudio en HSH HIV+ (septiembre 2012-marzo 2014, Hospital Fernández). Se recogió información demográfica, de HIV, HPV y prácticas sexuales. Se realizó citología anal, detección de HPV-AR (HC2 High-Risk HPV DNA, Digene®) y genotipificación en las muestras HPV-AR+ (Inno Lipa®, Fujirebio). Los pacientes firmaron consentimiento informado. Se indicó tratamiento según resultados. Resultados: Completaron el estudio 57 pacientes. Mediana de edad: 40 años (rango intercuartil [RIC]: 29-45); de CD4: 444 cels/mm3 (RIC: 345-568); 77% recibían tratamiento antirretroviral, 68% con carga viral no detectable. Citologías: negativas (24%); lesión intraepitelial de bajo grado (54%); lesión intraepitelial de alto grado (20%); ASCUS (2%). El 80% fue HPV-AR+. Los pacientes con diagnóstico de HPV-AR (p=0,006) y de lesión intraepitelial tuvieron CD4 <500 cels/mm3 con más frecuencia (p=0,030). Los pacientes con HPV-AR tuvieron mayor frecuencia de carga viral detectable (p=0,020, prueba de Fisher). El porcentaje de pacientes con uso consistente de preservativo fue mayor entre los pacientes sin lesión citológica (p=0,026). Genotipos de alto riesgo más frecuentes: HPV-16 (51%), HPV-31 (44%) y HPV-51 (40%); de bajo riesgo: HPV-6 (47%) y HPV-44 (35%).Conclusiones: Se encontró elevada frecuencia de lesión citológica (76%) y de HPV-AR (80%). Es necesario establecer estrategias de prevención en esta población incluyendo tamizaje, vacunación y promoción de sexo seguro.Palabras clave: HIV, lesión intraepitelial anal, HPV, citología anal, tamizaje de cáncer anal, hombres que tienen sexo con hombre
ntroduction: Anal cancer, associated with the infection with high risk Human Papillomavirus (HR-HPV), is very frequent among HIV+ men who have sex with men (MSM). Objective: To evaluate the frequency of HR-HPV infection, presence of HPV genotypes and HPV- associated lesions and associated factors.Methods: Study in HIV+ MSM (September 2012- March 2014, Hospital Fernández). Demographical, HIV, HPV and sexual behaviour information was collected. Cytology, HR-HPV detection (HC2 High-Risk HPV DNA, Digene ®) and genotyping was performed on samples positive for HR-HPV (Inno Lipa®, Fujirebio). All patients signed informed consent. Treatment was provided according to results.Results: Fifty-seven patients completed the study. Median age was 40 years old (interquartile range [IQR]: 29-45); median CD4 cell count: 444 cels/mm3 (IQR: 345-568); 77% were under ARV treatment, 68% with undetectable viral load. Cytology results: 24% negative, 54% low grade intraepithelial lesion, 20% high grade intraepithelial lesion, 2% ASCUS. Eighty percent were HR-HPV+. Patients with HR-HPV (p=0,006) and diagnosis of intraepithelial lesion had more frequent CD4 <500 cels/mm3 (p=0,030). Patients diagnosed with HR-HPV had a higher frequency of detectable viral load (p=0,020, prueba de Fisher). The percentage of patients with consistent condom use was higher among patients without cytological lesion (p=0,026).Most frequent high risk genotypes: HPV-16 (51%), HPV-31 (44%) and HPV-51 (40%); low risk genotypes HPV-6 (47%) and HPV-44 (35%).Conclusions: There was high frequency of cytological lesions (76%) and HR-HPV (80%). It is necessary to promote prevention strategies in this population including screening, vaccine and safe sex promotion
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Humanos , Masculino , Adulto , Persona de Mediana Edad , Neoplasias del Ano/prevención & control , Heridas y Lesiones/terapia , Infecciones por VIH/terapia , Infecciones por VIH/epidemiología , Control de Enfermedades Transmisibles , Infecciones por Papillomavirus/terapia , Infecciones por Papillomavirus/epidemiología , Sexo Inseguro/prevención & control , Minorías Sexuales y de GéneroRESUMEN
BACKGROUND: Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor 2 (HER2) which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC. METHODS: We retrospectively studied 86 HER2-positive breast cancer patients treated with trastuzumab and chemotherapy in the adjuvant setting. We explored the association of the IMPC component with clinicopathological parameters at diagnosis and its prognostic value. We compared MUC4 expression in IMPC with respect to other histological breast cancer subtypes by immunohistochemistry. RESULTS: IMPC, either as a pure entity or associated with invasive ductal carcinoma (IDC), was present in 18.6% of HER2-positive cases. It was positively correlated with estrogen receptor expression and tumor size and inversely correlated with patient's age. Disease-free survival was significantly lower in patients with IMPC (hazard ratio = 2.6; 95%, confidence interval 1.1-6.1, P = 0.0340). MUC4, a glycoprotein associated with metastasis, was strongly expressed in all IMPC cases tested. IMPC appeared as the histological breast cancer subtype with the highest MUC4 expression compared to IDC, lobular and mucinous carcinoma. CONCLUSION: In HER2-positive breast cancer, the presence of IMPC should be carefully examined. As it is often not informed, because it is relatively difficult to identify or altogether overlooked, we propose MUC4 expression as a useful biomarker to highlight IMPC presence. Patients with MUC4-positive tumors with IMPC component should be more frequently monitored and/or receive additional therapies.
Asunto(s)
Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/mortalidad , Carcinoma Papilar/mortalidad , Mucina 4/metabolismo , Receptor ErbB-2/metabolismo , Trastuzumab/farmacología , Adulto , Anciano , Antineoplásicos Inmunológicos , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Papilar/tratamiento farmacológico , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Estudios de Casos y Controles , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/inmunología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Objetivo: Realizar una revisión de las biopsias de nervio y músculo de pacientes con sospecha clínica de neuropatía vasculítica y correlacionarlas con los datos clínicos, de laboratorio y electrofisiológicos. Materiales y métodos: Fueron revisadas retrospectivamente las historias clínicas de pacientes sometidos a biopsia de nervio/músculo debido a sospecha clínica de neuropatía vasculítica en el Hospital General de Agudos Juan A. Fernández de la Ciudad Autónoma de Buenos Aires entre los años 1999 y 2011. Resultados: Se incluyeron 13 pacientes, 8 (61,54 por ciento) de sexo femenino y 5 (38,46 por ciento) de sexo masculino; la edad media fue de 58,85 +/- 15,02 años. Dos tercios de los casos presentaron mononeuropatía múltiple al diagnóstico y en 9 de 12 casos el patrón electromiográfico fue axonal. La anatomía patológica del nervio mostró vasculitis definida en 6 casos (46,15 por ciento) y probable sólo en uno (7,69 por ciento), mientras que la biopsia de músculo evidenció vasculitis en el 90 por ciento de los casos (p=0,077). En el subgrupo de pacientes con diagnóstico definitivo de vasculitis sistémica primaria, el 100 por ciento de las biopsias de músculo y el 62,5 por ciento de las biopsias de nervio resultaron positivas para neuropatía vasculítica (NPV). Conclusiones: La biopsia de nervio es el único procedimiento aceptado actualmente para el diagnóstico definitivo de neuropatía vasculítica. La biopsia combinada de nervio y músculo mostró una clara tendencia, aunque no significativa, hacia una mayor utilidad diagnóstica de neuropatía vasculítica que la biopsia de nervio aislada. Consideramos que el estudio de un mayor número de casos contribuirá a aclarar esta duda.
Objective: To review the nerve and the muscle biopsies from patients with clinical suspicion of vasculitic neuropathy and their correlation with clinical, laboratory and electrophysiologic studies. Materials and methods: We retrospectively reviewed the medical records of patients undergoing nerve/muscle biopsy due to clinical suspicion of vasculitic neuropathy at the Juan A. Fernandez General Hospital in the city of Buenos Aires between 1999 and 2011. Results: Thirteen patients, 8 (61.54 percent) female and 5 (38.46 percent) male, mean age 58.85 +/- 15.02 years, were included. Two thirds of the patients had multiple mononeuropathy at diagnosis, and 9 of 12 cases had axonal pattern in the electromyogram. The histopathology of the nerve showed definite vasculitis in 6 cases (46.15 percent) and probable vasculitis in only one (7.69 percent), whereas muscle biopsy showed vasculitis in 90 percent of cases (p=0.077). In the subgroup of patients with definite diagnosis of primary systemic vasculitis, 100 percent of muscle biopsies and 62.5 percent of nerve biopsies were diagnostic of vasculitis neuropathy. Conclusion: Nerve biopsy in the only currently accepted procedure for definitive diagnosis of vasculitic neuropathy. The combined nerve and muscle biopsy showed a clear trend, but not statistically significant toward increased the diagnostic yield of vasculitis neuropathy that isolated nerve biopsy. A large number of cases will clarify this issue.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/patología , Vasculitis/diagnóstico , Vasculitis/patología , BiopsiaRESUMEN
La cistitis enfisematosa es una rara condición caracterizada por la presencia de gas en el lumen y la pared de la vejiga como consecuencia de la colonización de microorganismos fermentadores. La mayoría de los casos se describen en mujeres de edad media con diabetes mellitus; es menos frecuente en pacientes inmunosuprimidos. A continuación presentamos un paciente con diagnóstico reciente de poliangeítis microscópica que desarrolló una cistitis enfisematosa como complicación del tratamiento inmunosupresor.
Emphysematous cystitis is a rare condition characterized by the presence of gas in the bladder wall and lumen result of the colonization by fermentative microorganisms. Most of the cases have been described in middle-age woman suffering from Diabetes Mellitus, being less frequently in immunosuppressive patients. We report here a patient with Microscopic Poliangeiitis who developed emphysematous cystitis as a complication of immunosuppressive therapy.