Aspectos prácticos sobre la determinación de PD-L1 en el tratamiento de carcinoma urotelial. Consenso del grupo de uropatología de la SEAP / Practical aspects of PD-L1 assessment in the treatment of urothelial carcinoma: Consensus of the uropathology group of the SEAP

La reciente llegada de nuevos fármacos de inmunoterapia para el tratamiento del carcinoma urotelial hace necesario establecer criterios para armonizar la determinación de PD-L1 mediante inmunohistoquímica como factor pronóstico y para la selección de pacientes a tratar. En este escenario, un grupo de uropatólogos de la Sociedad Española de Anatomía Patológica, junto con un oncólogo médico como colaborador externo subespecializado en urooncología, ha elaborado este documento de recomendaciones basadas en la evidencia disponible. En la determinación de PD-L1 son especialmente relevantes la selección de la muestra analizada, su procesamiento, la plataforma de inmunohistoquímica y anticuerpo empleados, así como el algoritmo que se aplique para la lectura. Todos estos aspectos deben indicarse en el informe de resultados, que debería poder ser fácilmente interpretable en un contexto de rápida evolución de terapias inmunológicas.(AU)

The recent addition of novel immunotherapy drugs for the treatment of urothelial carcinoma makes it necessary the establishment of criteria to harmonize the immunohistochemical assessment of PD-L1, both as a prognostic factor and for the selection of patients to be treated. In this scenario, a group of uropathologists from the Spanish Society of Pathological Anatomy, together with a medical oncologist as an external collaborator subspecialized in uro-oncology, have prepared this document of recommendations based on the available evidence. During PD-L1 assessment it is especially relevant the selection of the sample, its processing, the immunohistochemical platform and antibody used, and the algorithm applied in the interpretation of results. All these aspects must be indicated in the results report, which should be easily interpretable in a context of rapid evolution of immunological therapies.(AU)

[Practical aspects of PD-L1 assessment in the treatment of urothelial carcinoma: Consensus of the uropathology group of the SEAP]. / Aspectos prácticos sobre la determinación de PD-L1 en el tratamiento de carcinoma urotelial. Consenso del grupo de uropatología de la SEAP.

The recent addition of novel immunotherapy drugs for the treatment of urothelial carcinoma makes it necessary the establishment of criteria to harmonize the immunohistochemical assessment of PD-L1, both as a prognostic factor and for the selection of patients to be treated. In this scenario, a group of uropathologists from the Spanish Society of Pathological Anatomy, together with a medical oncologist as an external collaborator subspecialized in uro-oncology, have prepared this document of recommendations based on the available evidence. During PD-L1 assessment it is especially relevant the selection of the sample, its processing, the immunohistochemical platform and antibody used, and the algorithm applied in the interpretation of results. All these aspects must be indicated in the results report, which should be easily interpretable in a context of rapid evolution of immunological therapies.

Tumor glioneuronal leptomeníngeo difuso: diagnóstico y tratamiento con un caso ilustrativo / Diffuse leptomeningeal glioneuronal tumor: A review of diagnosis and management with an illustrative case

El tumor glioneuronal leptomeníngeo difuso es una entidad infrecuente, con un curso indolente; fue descrito en la clasificación de los tumores del sistema del sistema nervioso central de la OMS 2016. Presentamos el caso de un varón de 11 años que comienza con un cuadro clínico inespecífico de cefalea, dolor lumbosacro e hidrocefalia comunicante. En el curso clínico aparecen crisis epilépticas con lesiones nodulares en RM craneal; fue diagnosticado de meningitis tuberculosa y tratado con tuberclostáticos. Ante un deterioro clínico progresivo, a pesar del tratamiento, y empeoramiento de los hallazgos en RM craneoespinal, se le realiza biopsia cerebral y de leptomeninges que confirma el diagnóstico de tumor glioneuronal leptomeníngeo difuso. El tumor glioneuronal leptomeníngeo difuso debe incluirse en el diagnóstico diferencial de los cuadros que se presentan con hidrocefalia comunicante y lesiones leptomeníngeas. Se precisa un diagnóstico histológico precoz mediante biopsia para establecer un tratamiento adecuado (AU)

Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are a rare indolent neoplasm described in the 2016 WHO classification of tumors of the central nervous system (CNS). We describe a case of an 11 year old boy who initially presented intermittent headache, low back pain and communicating hydrocephalus, misdiagnosed as having tuberculous meningitis. Further clinical deterioration with seizures was observed and follow-up MRI showed further aggravation of leptomeningeal enhancement in the basal cisterns. Biopsy of the brain and leptomeninges revealed a diffuse leptomeningeal glioneuronal tumor. DLGNT should be considered in the differential diagnosis of conditions presenting as communicating hydrocephalus with nodular lesions and leptomeningeal enhancement. A timely histologic diagnosis through a biopsy of the brain is necessary to confirm the diagnosis (AU)

TFG-ß Nuclear Staining as a Potential Relapse Risk Factor in Early-Stage Non-Small-Cell Lung Cancer.

Nowadays, the impact of the tumor-immune microenvironment (TME) in non-small-cell lung cancer (NSCLC) prognosis and treatment response remains unclear. Thus, we evaluated the expression of PD-L1, tumor-infiltrating lymphocytes (TILs), and transforming growth factor beta (TGF-ß) in NSCLC to identify differences in TME, detect possible new prognostic factors, and assess their relationship. We retrospectively analyzed 55 samples from patients who underwent NSCLC surgery and had over a 5-year follow-up. PD-L1 expression was determined by immunohistochemistry following standard techniques. The presence of TILs was evaluated at low magnification and classified into two categories, "intense" and "non-intense". Cytoplasmic TGF-ß staining visualization was divided into four categories, and unequivocal nuclear staining in >1% of viable tumor cells was defined as "present" or "absent". Our aim was to identify differences in disease-free survival (DFS) and overall survival (OS). Tumor stage was the only objective prognostic factor for OS. PD-L1 expression and the presence of TILs had no prognostic impact, neither their combination. There seems to be a lower expression of PD-L1 and a higher expression of TILs in early stages of the disease. Our TGF-ß nuclear staining analysis was promising, since it was associated with worse DFS, revealing this protein as a possible prognostic biomarker of recurrence for resectable NSCLC.

Diffuse leptomeningeal glioneuronal tumor: A review of diagnosis and management with an illustrative case.

Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are a rare indolent neoplasm described in the 2016 WHO classification of tumors of the central nervous system (CNS). We describe a case of an 11 year old boy who initially presented intermittent headache, low back pain and communicating hydrocephalus, misdiagnosed as having tuberculous meningitis. Further clinical deterioration with seizures was observed and follow-up MRI showed further aggravation of leptomeningeal enhancement in the basal cisterns. Biopsy of the brain and leptomeninges revealed a diffuse leptomeningeal glioneuronal tumor. DLGNT should be considered in the differential diagnosis of conditions presenting as communicating hydrocephalus with nodular lesions and leptomeningeal enhancement. A timely histologic diagnosis through a biopsy of the brain is necessary to confirm the diagnosis.

Ventriculostomía y biopsia endoscópica de una masa pineal con hidrocefalia y diagnóstico final inesperado / Ventriculostomy and endoscopic biopsy of pineal mass with hydrocephalus and unexpected definitive diagnosis

Presentamos el caso de una paciente de 72 años de edad sin antecedentes de interés que consultó en urgencias por un cuadro de 2 semanas de evolución de alteración de la marcha, cefalea y vómitos. El TAC craneal reveló la presencia de hidrocefalia obstructiva secundaria a una lesión pineal con impronta en el tercer ventrículo. La resonancia magnética mostró, además de la lesión ya referida, otra más pequeña situada en el foramen de Lushcka derecho. Se llevó a cabo una ventriculostomía endoscópica del suelo del tercer ventrículo y la biopsia endoscópica de la lesión, cuyo resultado fue de metástasis compatible con carcinoma de pulmón. Se realizó un TAC toracoabdominopélvico que mostró una masa pulmonar compatible con el carcinoma primario. Se decidió tratamiento sistémico de la enfermedad. La paciente falleció 2 meses tras el diagnóstico

A 72-year-old female with no relevant medical history consulted in the emergency room for a two-week history of headache, vomiting and gait disturbance. Head CT scan revealed obstructive hydrocephalus secondary to a pineal mass with compression of the third ventricle. Magnetic Resonance showed another mass located in the right Lushcka foramen. Endoscopic third-ventriculostomy and biopsy of pineal mass were performed. Pathological analysis was consistent with metastasis of carcinoma. Full-body CT scan showed a lung mass related to primary carcinoma. The patient received systemic treatment for metastatic lung cancer. She died two months after diagnosis

Does Asymmetric Hearing Loss Affect the Ability to Understand in Noisy Environments?

OBJECTIVES: This study aimed to determine whether, in asymmetric hearing loss, the presence of an ear with a better or worse hearing threshold is related to either better or worse speech-in-noise (SiN) intelligibility. MATERIALS AND METHODS: A total of 618 subjects with different degrees of hearing loss were evaluated for their ability to understand SiN. A stepwise forward logistic regression analysis was performed to identify the factors that affect performance. The influencing factors of very high or very low performance were determined. RESULTS: Age, especially after 70 years of age, and hearing loss, especially from moderate hearing loss, negatively influence SiN intelligibility. Remarkably high intelligibility was identified in subjects with a contralateral ear presenting a better auditory threshold. CONCLUSION: Although age and hearing loss are known factors that affect SiN intelligibility, the presence of a healthy contralateral ear is presented as the first description of preservation of SiN hearing ability.

Ventriculostomy and endoscopic biopsy of pineal mass with hydrocephalus and unexpected definitive diagnosis. / Ventriculostomía y biopsia endoscópica de una masa pineal con hidrocefalia y diagnóstico final inesperado.

A 72-year-old female with no relevant medical history consulted in the emergency room for a two-week history of headache, vomiting and gait disturbance. Head CT scan revealed obstructive hydrocephalus secondary to a pineal mass with compression of the third ventricle. Magnetic Resonance showed another mass located in the right Lushcka foramen. Endoscopic third-ventriculostomy and biopsy of pineal mass were performed. Pathological analysis was consistent with metastasis of carcinoma. Full-body CT scan showed a lung mass related to primary carcinoma. The patient received systemic treatment for metastatic lung cancer. She died two months after diagnosis.

Normative data for static balance testing in healthy individuals using open source computerized posturography.

PURPOSE: Computerized posturography is the gold standard for balance assessment. Because of the great cost and dimensions of commercial equipments, low-cost and portable devices have been developed and validated, such as RombergLab, a software in open source term which works connected with a low-cost force platform. The objective of this study was to obtain normative posturography data using this software. METHODS: A multicentric prospective and descriptive study, with 350 healthy participants, was designed. Static postural stability (measured using the modified clinical test of sensory interaction on balance) was evaluated using the software connected to the force platform. Using the confidence ellipse area (CEA) in each condition, global equilibrium score (GES) was calculated and adjusted for significant variable factors using cluster analysis. RESULTS: Mean (SD) GES was 0.72 (0.22). Age (p < 0.01), height (p < 0.01) and recruitment center (p < 0.05) were found as influence factors for GES. Cluster analysis obtained 16 groups stratified by age and height. GES decreases with age and height (p < 0.005). No significant interaction of age nor height was found with GES in these clusters (p > 0.05). After correction for height and age, GES was no longer influenced by the recruitment center (p > 0.05). CONCLUSIONS: With the introduction of the global equilibrium score values of the present study into the software, we consider RombergLab v1.3 a reference posturography tool for healthy individuals. Further studies are needed for validating it as a suitable instrumented test for screening between healthy and pathologic subjects and its reliability over time for the follow-up of patients.

Fracaso renal agudo secundario a nefritis intersticial granulomatosa asociada al tratamiento con tramadol / Acute Kidney Injury due to granulomatous interstitial nephritis induced by tramadol administration

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Low-grade myofibroblastic sarcoma of the larynx: a case report / Sarcoma miofibroblástico de bajo grado en laringe: reporte de un caso

Low-grade myofibroblastic sarcoma is a rare neoplasm, with an incidence of less than 1% and a predilection for the head and neck area. We report a case occurring in a 55 year-old male and in an unusual location: the anterior commissure of the larynx. The patient presented with short-term dysphonia. A nodular lesion on the right vocal cord was detected and a biopsy and subsequent resection of the mass was performed. The nodule consisted of a spindle cell fascicular proliferation in a dense collagenous matrix. Moderate atypia, mitotic activity (>10X10HPF) and a proliferation index of 10% were noted. Immunohistochemistry showed positivity for vimentin, muscle-specific actin (HHF35) and negativity fordesmin, ALK, p53, cytokeratins (AE1/AE3, 5/6 and 18), EMA, GFAP, S100, CD34, CD68 and CD99 (AU)

El sarcoma miofibroblástico de bajo grado es una neoplasia rara con predilección por cabeza y cuello, con una incidencia menor del 1%. Reportamos el caso de un varón de 55 años, en comisura anterior de laringe, un sitio infrecuente. El paciente aquejaba disfonía de corta duración, detectándose un nódulo en cuerda vocal derecha, que fue extirpado. Una proliferación celular fusiforme, fasciculada, sobre una matriz colagenosa densa. Atipia moderada, actividad mitótica (>10× CGA), con un índice de proliferación celular del 10%, fue observada. La celularidad demostró positividad para vimentina, actina músculo específica, con negatividad para desmina, ALK, p53, citoqueratinas (AE1/AE3, 5/6 y 18), EMA, PAGF, S100, CD34, CD68 y CD99 (AU)

Control of vertigo after intratympanic corticoid therapy for unilateral Ménière's disease: a comparison of weekly versus daily fixed protocols.

OBJECTIVE: This study aimed to evaluate the long-term effects of intratympanic corticoid therapy on vertigo control and hearing changes. STUDY DESIGN: The study design was retrospective. SETTING: Tertiary medical centers. PATIENTS: Fifty-six patients with definite unilateral Ménière's disease, diagnosed using the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines, were included. Twenty-two patients were treated with a fixed protocol of 3 consecutive daily intratympanic injections of a 4 mg/ml dexamethasone commercial preparation. Thirty-four patients were treated with a fixed protocol of 3 consecutive weekly injections of the same preparation. MAIN OUTCOME MEASURE: The 1995 AAO-HNS criteria for reporting treatment outcome in MD were used. The treatment results were expressed in terms of vertigo control. A Kaplan-Meier analysis was used to evaluate the control of vertigo over a 2-year period. Separate curves were created depending on the protocol used and the class of vertigo control obtained. RESULTS: Complete vertigo control (class A) was achieved in 40.9% and 44.1% of patients on the daily and weekly protocols, respectively. Substantial vertigo control was obtained in an additional 18.2% and 14.7% of patients on the daily and weekly protocols, respectively. No significant differences were found between the 2 fixed protocols. CONCLUSION: Intratympanic dexamethasone (4 mg/ml) perfusion provides an alternative treatment for definite Ménière's disease. The Kaplan-Meier analysis was useful for analyzing the control of vertigo and the recurrence of Ménière's disease.

Time course of episodes of definitive vertigo in Meniere's disease.

OBJECTIVE: To evaluate the frequency and duration of episodes of definitive vertigo in Ménière's disease. DESIGN: Prospective longitudinal study. SETTING: Multiple tertiary referral centers. PATIENTS: Five hundred ten individuals from 8 hospitals that met the American Academy of Otolaryngology-Head and Neck Surgery diagnostic criteria for definitive Ménière's disease. INTERVENTION: Conservative treatment. MAIN OUTCOME MEASURE: Frequency and duration of episodes of definitive vertigo during follow-up. RESULTS: Ménière's disease affects both sexes and both ears equally, with onset generally in the fourth decade of life. The number of episodes of vertigo is greater in the first few years of the disease. Although episodes of vertigo that last longer than 6 hours are less frequent than shorter episodes, they occur with similar frequency throughout the natural course of the disease. The percentage of patients without episodes of vertigo increases as the disease progresses, and 70% of patients who did not have an episode of vertigo for 1 year will continue to be free of episodes during the following year. Thus, there is a relationship between the frequency of episodes in consecutive years, although this association decreases rapidly as the number of years increases. CONCLUSION: The frequency of definitive episodes of vertigo in Ménière's disease decreased during follow-up, and many individuals reached a steady-state phase free of vertigo.

Síndrome febril de larga evolución y demencia / Prolonged febrile syndrome and dementia

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