RESUMEN
BACKGROUND: Forty to fifty percent of patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) relapse despite multimodal treatment. Circulating tumor DNA (ctDNA) has the potential to detect minimal residual disease (MRD) after curative-intent therapy and to identify earlier which patients will progress. We developed a tumor-agnostic plasma ctDNA assay to detect MRD in unselected LA SCCHN with the aim of predicting progression-free survival (PFS) and overall survival without the need for tumor sequencing. PATIENTS AND METHODS: A 26-gene next-generation sequencing panel was constructed that included the most frequently mutated genes in SCCHN and two HPV-16 genes. MRD was assessed in each patient through an in-house informatic workflow informed by somatic mutations identified in the corresponding pre-treatment plasma sample. The presence of MRD was defined as the detection of ctDNA in one plasma sample collected within 1-12 weeks of the end of curative treatment. The primary endpoint was the PFS rate at 2 years. At least 32 patients were planned for inclusion with the hypothesis that PFS at 2 years was >80% in MRD-negative patients and <30% in MRD-positive patients (α = 0.05, ß = 0.9). RESULTS: We sequenced DNA from 116 plasma samples derived from 53 LA SCCHN patients who underwent curative-intent treatment. ctDNA was detected in 41/53 (77%) patients in the pre-treatment samples. Out of these 41 patients, 17 (41%) were MRD positive after treatment. The 2-year PFS rate was 23.53% (9.9% to 55.4%) and 86.6% (73.4% to 100%) in MRD-positive and MRD-negative patients, respectively (P < 0.05). Median survival was 28.37 months (14.30 months-not estimable) for MRD-positive patients and was not reached for the MRD-negative cohort (P = 0.011). CONCLUSIONS: Our ctDNA assay detects MRD in LA SCCHN and predicts disease progression and survival without the need for tumor sequencing, making this approach easily applicable in daily practice.
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ADN Tumoral Circulante , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , ADN Tumoral Circulante/genética , Neoplasia Residual/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapia , Biomarcadores de Tumor/genéticaRESUMEN
Paraneoplastic pemphigus is a rare autoimmune blistering disease generally associated with malignancy. The clinical presentation consists typically of painful and diffuse erosive stomatitis that may be accompanied by polymorphic skin lesions and systemic involvement. Diagnosis is based on clinical manifestations and confirmed by histology and immunological testing. The current first-line treatment is systemic corticosteroids and adjuvant therapies, including immunosuppressive agents. We report a case of buccal paraneoplastic pemphigus resistant to ibrutinib and rituximab successfully treated with azathioprine and polyclonal immunoglobulins.
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Enfermedades Autoinmunes , Síndromes Paraneoplásicos , Pénfigo , Enfermedades Cutáneas Vesiculoampollosas , Humanos , RituximabRESUMEN
BACKGROUND: Digital dermoscopy has been shown to permit an earlier detection of melanoma. However, few studies have investigated its added value in reducing unnecessary excisions in everyday clinical practice. OBJECTIVES: To compare, in daily practice, the efficiency of three dermoscopy methods: dermoscopy alone with little training, dermoscopy alone with adequate training and dermoscopy with adequate training and access to digital dermoscopy, and to confirm the safety of this latter approach. METHODS: Thirty-six dermatologists working without digital dermoscopy were divided into two groups according to their training in dermoscopy. The third group constituted of two dermatologists working in a pigmented lesion clinic with access to the digital dermoscopy technique and eight additional dermatologists working in the same dermatology department. These 46 dermatologists included all presumed melanocytic lesions excised over a period of 1 year. The primary endpoint was the melanoma/nonmelanoma ratio (M/NM-R); secondary endpoints were the ratio of 'problem' naevi to common naevi (PN/CN-R), specificity and sensitivity for the diagnosis of melanoma, in situ/invasive melanoma ratio, and the mean Breslow thickness. RESULTS: In total, 1865 excised lesions, including 231 melanomas, were included. In the digital dermoscopy availability group (DD-G) the M/NM-R was significantly better (1/2.43), as was the PN/CN-R (1/1.48) (P < 0.001 in both cases). The specificity was significantly higher in the DD-G and significantly higher for trained examiners as compared with examiners with little training. More that one-third of all melanomas discovered by digital dermoscopy were in situ, and the mean Breslow thickness was 0.32 mm for the invasive ones. CONCLUSIONS: The reduction of unnecessary excisions when using digital dermoscopy compared with dermoscopy alone in our study suggests that access to digital dermoscopy offers a better management of pigmented lesions in daily practice. The high number of early lesions diagnosed by this technique confirms that its use is safe.
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Dermoscopía/métodos , Melanoma/diagnóstico , Nevo Pigmentado/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Dermoscopía/normas , Detección Precoz del Cáncer/métodos , Educación Médica Continua , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Interpretación de Imagen Asistida por Computador/normas , Masculino , Melanocitos , Melanoma/cirugía , Persona de Mediana Edad , Nevo Pigmentado/cirugía , Factores de Riesgo , Sensibilidad y Especificidad , Neoplasias Cutáneas/cirugía , Adulto JovenRESUMEN
We report a case of a 50-year old post-menopausal woman who was admitted because of a lump in the upper external quadrant of her left breast. The definitive diagnosis of periductal stromal tumor was retained after histopathological examination. Periductal stromal tumor is a rare tumor with distinct morphological features. The clinical evolution and the prognosis are relatively similar to the phyllodes tumor.
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Neoplasias de la Mama/patología , Antígenos CD34/análisis , Neoplasias de la Mama/cirugía , Diagnóstico Diferencial , Femenino , Fibroadenoma/patología , Humanos , Persona de Mediana Edad , Tumor Filoide/patología , Posmenopausia , Proteínas Proto-Oncogénicas c-kit/análisis , Células del Estroma/patologíaRESUMEN
INTRODUCTION: The Locked-In syndrome (LIS) is defined by: (i) the presence of sustained eye opening (bilateral ptosis should be ruled out as a complicating factor); (ii) preserved awareness; (iii) aphonia or hypophonia; (iv) quadriplegia or quadriparesis; and (v) a primary mode of communication that uses vertical or lateral eye movement or blinking. Acute ventral pontine lesions are its most common cause. Following such brainstem lesions patients may remain comatose for some time and then gradually awaken, remaining paralyzed and voiceless, superficially resembling the vegetative state. BACKGROUND: It has been shown that more than half of the time physicians fail to recognize early signs of awareness in LIS. Given appropriate medical care, life expectancy may be several decades but the chances of good motor recovery remain small. Eye-controlled computer technology now allows LIS patients to communicate and control their environment. Recent studies show that most LIS patients self-report meaningful quality of life and the demand for euthanasia is infrequent. CONCLUSION: Patients suffering from LIS should not be denied the right to die--and to die with dignity--but also they should not be denied the right to live--and to live with dignity and the best possible pain and symptom management and revalidation.
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Blefaroptosis/etiología , Parpadeo/fisiología , Comunicación , Cuadriplejía/fisiopatología , Blefaroptosis/fisiopatología , Progresión de la Enfermedad , Humanos , Pronóstico , Cuadriplejía/diagnóstico , Cuadriplejía/etiología , Cuadriplejía/mortalidad , Cuadriplejía/psicología , Derecho a MorirRESUMEN
The locked-in syndrome (LIS) is a severe condition originated by a ventral pons lesion causing quadriplegia and anarthria but with a preserved consciousness. LIS seems to be a well defined clinical picture, although different problems still persist, such as the diagnosis as it is usually mistaken for akinetic mutism and a vegetative state; the unclear prognosis, because of the patient's psychological state and the lack of information and data concerning the different types of available treatment and the need for results. Rehabilitation is a challenge for physicians, new methods and techniques of specialized treatments for these patients are opening a new future that will allow us to abandon the initial pessimism. A more efficient rehabilitation of these patients depends on the intensity of the rehabilitation, the multidisciplinary approach, and duration of the treatment.
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Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/rehabilitación , Cuadriplejía/diagnóstico , Cuadriplejía/rehabilitación , Trastornos del Conocimiento/etiología , Diagnóstico Diferencial , Humanos , Enfermedades Neuromusculares/diagnóstico , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Pronóstico , Cuadriplejía/complicaciones , Índice de Severidad de la EnfermedadRESUMEN
Eosinophilic cellulitis (Wells' syndrome) is a rare condition of unknown aetiopathogenesis and is characterized by erythemal plaques and a histological picture of eosinophilic infiltration of the dermis with 'flame' figures. Here we describe a patient with the papulonodular variant of eosinophilic cellulitis associated with an unusual hepatic dysfunction.
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Celulitis (Flemón)/patología , Eosinofilia/patología , Piel/patología , Celulitis (Flemón)/complicaciones , Eosinofilia/complicaciones , Eosinófilos/patología , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , SíndromeAsunto(s)
Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , Metilprednisolona/administración & dosificación , Tuberculosis Pulmonar/diagnóstico , Antituberculosos/uso terapéutico , Diagnóstico Diferencial , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
Aphasia recovery may depend on right hemisphere or non-lesioned left hemisphere structures, pre-morbid brain language organization, and de novo learning of language. Here we review the brain imaging evidence supporting these different hypotheses. CT-scan studies have investigated the prognosis value of size and site of left hemisphere lesions. The size of the lesion is a global but not an individual predictor of the initial severity and subsequent recovery of aphasia. Studies on the site of the lesion have given different results for verbal expression and comprehension. There is no consensus on a single critical site for recovery of verbal expression in non-fluent aphasia, which may depend on sub-cortical more than cortical extend of the lesion. Conversely the extend of the lesion in the superior temporal gyrus emerges as a critical negative factor for comprehension recovery. Rest measurements of brain metabolism have consistently shown that aphasia severity depends much more on the degree of dysfunction of language-related areas in the left hemisphere than on the site of the lesion it-self. This suggests that aphasia recovery may depend on metabolic dysfunction recovery in peri-lesional structures. More recently, activation studies have shown consistent right hemisphere activation during language tasks in aphasic subjects, but their role in recovery remains debated. It is likely limited, and may depend on atypical pre-morbid language lateralization. Left hemisphere activations are also found in aphasic patients. They are often relocalized in peri-lesional areas, and emerge in most studies as the main factor of aphasia recovery.
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Afasia/rehabilitación , Encéfalo/patología , Afasia/diagnóstico , Encéfalo/diagnóstico por imagen , Lateralidad Funcional/fisiología , Humanos , Imagen por Resonancia Magnética , Magnetoencefalografía , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos XRESUMEN
Progressive development of a lobulated osteolytic lesion of the left calcaneus was observed in a 28-year-old woman. The bone tumor was associated with multiple lung nodules and later with a few small nodular liver lesions. A histological and immunochemical diagnosis of epithelioid hemangioendothelioma was obtained by bone tumor resection and thoracoscopic lung biopsy. Imaging aspects are reported with emphasis on its multifocality.
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Neoplasias Óseas/patología , Calcáneo , Hemangioendotelioma Epitelioide/secundario , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Adulto , Neoplasias Óseas/diagnóstico por imagen , Femenino , Hemangioendotelioma Epitelioide/diagnóstico por imagen , Humanos , Tomografía Computarizada por Rayos XRESUMEN
We report the case of an 84-year-old woman who was initially admitted to the emergency room of our institution for frank dehydration caused by acute and severe secretory diarrheas along with acidosis and hypokalemia. After extensive gastrointestinal investigations, the etiology of the diarrhea remained unclear. Because clinical symptoms and ionogram parameters worsened, despite intravenous fluids and electrolyte replacement, an abdominal CT scan was performed and unexpectedly revealed a 4.5-cm mass in the right adrenal gland. Several separate 24-hour urine catecholamines were shown to be highly elevated. The diagnosis of pheochromocytoma was confirmed by MIBG scintigraphy and MRI. Before the admission, the patient never experienced symptoms suggestive of pheochromocytoma, except dry mouth and fear of impending death on several occasions. After 2 weeks, the diarrhea stopped abruptly and spontaneously without specific medication but after adequate rehydration. The patient subsequently underwent surgical removal of the adrenal medullary mass. Postoperatively, urinary catecholamines returned to normal values. Immunohistochemical study of the tumor confirmed the diagnosis of pheochromocytoma and revealed the presence of VIP-positive cells organized as islets in scattered areas of the tissue. This case illustrates the protean mode of presentation of pheochromocytoma, as well as the ability of medullary neural crest-derived cells to produce various neuropeptides potentially responsible for a large variety of symptoms.
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Neoplasias de las Glándulas Suprarrenales/complicaciones , Diarrea/etiología , Feocromocitoma/complicaciones , Enfermedad Aguda , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Feocromocitoma/diagnóstico por imagen , Feocromocitoma/patología , RadiografíaRESUMEN
Time is a fundamental dimension of cognition. It is expressed in the sequential ordering of individual elements in a wide variety of activities such as language, motor control or in the broader domain of long range goal-directed actions. Several studies have shown the importance of the frontal lobes in sequencing information. The question addressed in this study is whether this brain region hosts a single supramodal sequence processor, or whether separate mechanisms are required for different kinds of temporally organised knowledge structures such as syntax and action knowledge. Here we show that so-called agrammatic patients, with lesions in Broca's area, ordered word groups correctly to form a logical sequence of actions but they were severely impaired when similar word groups had to be ordered as a syntactically well-formed sentence. The opposite performance was observed in patients with dorsolateral prefrontal lesions, that is, while their syntactic processing was intact at the sentence level, they demonstrated a pronounced deficit in producing temporally coherent sequences of actions. Anatomical reconstruction of lesions from brain scans revealed that the sentence and action grammar deficits involved distinct, non-overlapping sites within the frontal lobes. Finally, in a third group of patients whose lesions encompassed both Broca's area and the prefrontal cortex, the two types of deficits were found. We conclude that sequence processing is specific to knowledge domains and involves different networks within the frontal lobes.
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Lóbulo Frontal/fisiología , Trastornos del Lenguaje/fisiopatología , Análisis de Varianza , Afasia de Broca/etiología , Afasia de Broca/fisiopatología , Corteza Cerebral/fisiopatología , Infarto Cerebral/complicaciones , Infarto Cerebral/fisiopatología , Femenino , Lóbulo Frontal/fisiopatología , Humanos , Trastornos del Lenguaje/etiología , Pruebas del Lenguaje , Masculino , Persona de Mediana Edad , Análisis y Desempeño de Tareas , Pruebas de Asociación de PalabrasRESUMEN
We report the case of a patient with intestinal ischaemia and necrosis resulting from vasculitis of mesenteric veins and their intramural tributaries. This patient was otherwise healthy, had no prior history of inflammatory bowel disease nor clinical evidence of extra intestinal involvement or systemic vasculitis, and since four years, was treated with hydroxyethyl rutoside (Venoruton). He recovered completely after segmental resection of the affected portion of the bowel and had no recurrence of intestinal symptoms on follow-up of up to three years. The histopathological diagnostic hallmarks of this clinical entity are extensive lesions of lymphocytic phlebitis associated with thrombi of different ages and focal fibrinoid necrosis while arteries and arterioles are not affected. This unusual form of vasculitis affecting veins only is very rare and its etiology unknown.
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Colon/irrigación sanguínea , Intestino Delgado/irrigación sanguínea , Flebitis/complicaciones , Anciano , Colon/patología , Colon/cirugía , Humanos , Íleon/irrigación sanguínea , Íleon/cirugía , Intestino Delgado/patología , Intestino Delgado/cirugía , Isquemia/etiología , Isquemia/cirugía , Linfocitos/patología , Masculino , Oclusión Vascular Mesentérica/complicaciones , Venas Mesentéricas , Necrosis , Flebitis/patología , Flebitis/cirugíaRESUMEN
We examined mechanisms of recovery from aphasia in seven nonfluent aphasic patients, who were successfully treated with melodic intonation therapy (MIT) after a lengthy absence of spontaneous recovery. We measured changes in relative cerebral blood flow (CBF) with positron emission tomography (PET) during hearing and repetition of simple words, and during repetition of MIT-loaded words. Without MIT, language tasks abnormally activated right hemisphere regions, homotopic to those activated in the normal subject, and deactivated left hemisphere language zones. In contrast, repeating words with MIT reactivated Broca's area and the left prefrontal cortex, while deactivating the counterpart of Wernicke's area in the right hemisphere. The recovery process induced by MIT in these patients probably coincides with this reactivation of left prefrontal structures. In contrast, the right hemisphere regions abnormally activated during simple language tasks seem to be associated with the initial persistence of the aphasia. This study supports the idea that abnormal activation patterns in the lesioned brain are not necessarily related to the recovery process.
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Afasia/diagnóstico por imagen , Afasia/terapia , Musicoterapia , Adulto , Encéfalo/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Tomografía Computarizada de EmisiónRESUMEN
Aphemia, also called anarthria or severe apraxia of speech, is a rare disorder of speech production usually resulting from vascular lesions affecting the inferior premotor cortex of the left hemisphere. A patient presenting with aphemia as the sole manifestation of primary progressive aphasia (PPA) is reported.
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Afasia de Broca/fisiopatología , Afasia de Broca/psicología , Femenino , Humanos , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
What is knowable concerning the lived experience and the psychopathology of patients during the border state between coma and waking? The waking up period appears divided in two parts: "apparent incommunicability" and "waking in strangeness". A pluridisciplinary follow-up seems necessary for patients beginning with the neurosurgical reanimation process.
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Coma/psicología , Cuidados Críticos/psicología , Vigilia , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Neurocirugia , Comunicación no Verbal/psicología , Relaciones Enfermero-PacienteRESUMEN
Benign gastric tumours and pseudotumours have often been a cause of confusion not only diagnostically but also in terms of treatment, since their significance varies with the histologic type. We try to provide a comprehensive classification scheme dividing gastric benign tumours and pseudotumours in 3 major categories: epithelial, mesenchymatous and dysembryoplastic. We review the clinical significance of the subcategories.
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Neoplasias Gástricas/patología , Coristoma/patología , Coristoma/cirugía , Fibroma/patología , Fibroma/cirugía , Humanos , Pólipos Intestinales/patología , Pólipos Intestinales/cirugía , Leiomioma/patología , Leiomioma/cirugía , Lipoma/patología , Lipoma/cirugía , Páncreas , Neoplasias Gástricas/cirugíaRESUMEN
A 77 year old right handed male was blind since the age of 2. He presented with an infarction involving the territory of the left middle cerebral artery involving the temporal and the inferior parietal lobes. He had learned to read and write language as well as read and write music in braille, ultimately becoming a famous organist and composer. There were no motor or sensory deficits. Wernicke's aphasia with jargonaphasia, major difficulty in repetition, anomia and a significant comprehension deficit without word deafness was present; verbal alexia and agraphia in braille were also present. There was no evidence of amusia. He could execute in an exemplary fashion pieces of music for the organ in his repertory as well as improvise. All his musical capabilities: transposition, modulation, harmony, rythm, were preserved. The musical notation in braille remained intact: he could read by touch and play unfamiliar scores, he could also read and sing the musical notes, he could copy and write a score. Nine months after the stroke his aphasia remained unchanged. Nevertheless he composed pieces for the organ which were published. Such data highly suggest the independence of linguistic and musical competences, defined as the analysis and organization of sounds according to the rules of music. This independence in an extremely talented musician leads to a discussion of the role of the right hemisphere in the anatomical-functional processes at the origin of musical competence. The use of braille in which the same constellations of dots correspond either to letters of the alphabet or musical notes supports the independence between language and music.