EEG before chimeric antigen receptor T-cell therapy and early after onset of immune effector cell-associated neurotoxicity syndrome.

BACKGROUND: Immune effector cell-associated neurotoxicity syndrome (ICANS) is common after chimeric antigen receptor T-cell (CAR-T) therapy. OBJECTIVE: This study aimed to assess the impact of preinfusion electroencephalography (EEG) abnormalities and EEG findings at ICANS onset for predicting ICANS risk and severity in 56 adult patients with refractory lymphoma undergoing CAR-T therapy. STUDY DESIGN: EEGs were conducted at the time of lymphodepleting chemotherapy and shortly after onset of ICANS. RESULTS: Twenty-eight (50%) patients developed ICANS at a median time of 6 days after CAR-T infusion. Abnormal preinfusion EEG was identified as a risk factor for severe ICANS (50% vs. 17%, P = 0.036). Following ICANS onset, EEG abnormalities were detected in 89% of patients [encephalopathy (n = 19, 70%) and/or interictal epileptiform discharges (IEDs) (n = 14, 52%)]. Importantly, IEDs seemed to be associated with rapid progression to higher grades of ICANS within 24 h. CONCLUSIONS: If confirmed in a large cohort of patients, these findings could establish the basis for modifying current management guidelines, enabling the identification of patients at risk of neurotoxicity, and providing support for preemptive corticosteroid use in patients with both initial grade 1 ICANS and IEDs at neurotoxicity onset, who are at risk of neurological impairment.

Development and validation of an image biomarker to identify metabolic dysfunction associated steatohepatitis: MR-MASH score.

BACKGROUND AND AIMS: Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) requires histology. In this study, a magnetic resonance imaging (MRI) score was developed and validated to identify MASH in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Secondarily, a screening strategy for MASH diagnosis was investigated. METHODS: This prospective multicentre study included 317 patients with biopsy-proven MASLD and contemporaneous MRI. The discovery cohort (Spain, Portugal) included 194 patients. NAFLD activity score (NAS) and fibrosis were assessed with the NASH-CRN histologic system. MASH was defined by the presence of steatosis, lobular inflammation, and ballooning, with NAS ≥4 with or without fibrosis. An MRI-based composite biomarker of Proton Density Fat Fraction and waist circumference (MR-MASH score) was developed. Findings were afterwards validated in an independent cohort (United States, Spain) with different MRI protocols. RESULTS: In the derivation cohort, 51% (n = 99) had MASH. The MR-MASH score identified MASH with an AUC = .88 (95% CI .83-.93) and strongly correlated with NAS (r = .69). The MRI score lower cut-off corresponded to 88% sensitivity with 86% NPV, while the upper cut-off corresponded to 92% specificity with 87% PPV. MR-MASH was validated with an AUC = .86 (95% CI .77-.92), 91% sensitivity (lower cut-off) and 87% specificity (upper cut-off). A two-step screening strategy with sequential MR-MASH examination performed in patients with indeterminate-high FIB-4 or transient elastography showed an 83-84% PPV to identify MASH. The AUC of MR-MASH was significantly higher than that of the FAST score (p < .001). CONCLUSIONS: The MR-MASH score has clinical utility in the identification and management of patients with MASH at risk of progression.

Meta-Analysis of Extracellular Matrix Dynamics after Myocardial Infarction Using RNA-Sequencing Transcriptomic Database.

Extracellular matrix (ECM) changes after myocardial infarction (MI) need precise regulation, and next-generation sequencing technologies provide omics data that can be used in this context. We performed a meta-analysis using RNA-sequencing transcriptomic datasets to identify genes involved in post-MI ECM turnover. Eight studies available in Gene Expression Omnibus were selected following the inclusion criteria. We compare RNA-sequencing data from 92 mice submitted to permanent coronary ligation or sham, identifying differentially expressed genes (p-value < 0.05 and Log2FoldChange ≥ 2). Functional enrichment analysis was performed based on Gene Ontology biological processes (BPs). BPs implicated in response to extracellular stimulus, regulation of ECM organization, and ECM disassembly were detected soon after ischemia onset. ECM disassembly occurred between days one to seven post-MI, compared with ECM assembly from day seven onwards. We identified altered mRNA expression of 19 matrix metalloproteinases and four tissue inhibitors of metalloproteinases at post-infarcted ECM remodeling and altered transcriptomic expression of 42 genes encoding 26 collagen subunits at the fibrotic stage. To our knowledge, this is the first meta-analysis using RNA-sequencing datasets to evaluate post-infarcted cardiac interstitium healing, revealing previously unknown mechanisms and molecules actively implicated in ECM remodeling post-MI, which warrant further validation.

[Three cases of urachal cyst in adults]. / Quistes de uraco en adultos. Presentación de 3 casos y revisión de la literatura.

The urachus is a thick fibrous cord that appears in the fifth month of pregnancy as a result of the allantois obliteration. Urachal cysts occur as a result of a defect in the obliteration of the duct, anomaly detected mainly in children and very rarely in adults. We present three cases of urachal cysts in adults, one of them detected during the study of abdominal pain and the other two, found incidentally during the study of other pathologies. In any case the possibility of urachal cysts was clinically suspected. Histologically, these lesions are lined by epithelium of urothelial type with expression of CK7, CK20, CK5/6, P63 and GATA3. The diagnosis of urachal cysts certainty lies in the histopathological study where the morphology, immunohistochemistry and a proper clinical-pathological correlation, allow to differentiate it from other more frequent abdominal cystic lesions in adults.

Quistes de uraco en adultos. Presentación de 3 casos y revisión de la literatura / Three cases of urachal cyst in adults

El uraco es un grueso cordón fibroso que aparece a partir del quinto mes de gestación como consecuencia de la obliteración de la alantoides. Los quistes de origen uracal se producen como consecuencia de un defecto en la obliteración de dicho conducto, anomalía que se detecta principalmente en niños y raramente en adultos. Presentamos 3 casos de quistes uracales en adultos, uno de ellos detectado durante el estudio de dolor abdominal y los otros 2 hallados de forma incidental durante el estudio de otras patologías. En ningún caso se sospechó clínicamente la posibilidad de quistes uracales. Histológicamente, estas lesiones se encuentran revestidas por epitelio de tipo urotelial con expresión de CK7, CK20, CK5/6, P63 y GATA3. El diagnóstico de certeza recae en el estudio histopatológico donde la morfología, la inmunohistoquímica y un adecuado correlato clínico-patológico, permiten diferenciarlo de otras lesiones quísticas mucho más frecuentes en el adulto.(AU)

The urachus is a thick fibrous cord that appears in the fifth month of pregnancy as a result of the allantois obliteration. Urachal cysts occur as a result of a defect in the obliteration of the duct, anomaly detected mainly in children and very rarely in adults. We present three cases of urachal cysts in adults, one of them detected during the study of abdominal pain and the other two, found incidentally during the study of other pathologies. In any case the possibility of urachal cysts was clinically suspected. Histologically, these lesions are lined by epithelium of urothelial type with expression of CK7, CK20, CK5/6, P63 and GATA3. The diagnosis of urachal cysts certainty lies in the histopathological study where the morphology, immunohistochemistry and a proper clinical-pathological correlation, allow to differentiate it from other more frequent abdominal cystic lesions in adults.(AU)

Srebf2 Locus Overexpression Reduces Body Weight, Total Cholesterol and Glucose Levels in Mice Fed with Two Different Diets.

Macronutrients represent risk factors for hyperlipidemia or diabetes. Lipid alterations and type 2 diabetes mellitus are global health problems. Overexpression of sterol regulatory element-binding factor (Srebf2) in transgenic animals is linked to elevated cholesterol levels and diabetes development. We investigated the impact of increased Srebf2 locus expression and the effects of control and high-fat, high-sucrose (HFHS) diets on body weight, glucose and lipid metabolisms in transgenic mice (S-mice). Wild type (WT) and S-mice were fed with both diets for 16 weeks. Plasma glucose, insulin and lipids were assessed (n = 25). Immunostainings were performed in liver, pancreas and fat (N = 10). Expression of Ldlr and Hmgcr in liver was performed by RT-PCR (N = 8). Control diet: S-mice showed reduced weight, insulin, total and HDL cholesterol and triglycerides (TG). HFHS diet widened differences in weight, total and HDL cholesterol, insulin and HOMA index but increased TG in S-mice. In S-mice, adipocyte size was lower while HFHS diet produced lower increase, pancreatic ß-cell mass was lower with both diets and Srebf2, Ldlr and Hmgcr mRNA levels were higher while HFHS diet produced a rise in Srebf2 and Hmgcr levels. Srebf2 complete gene overexpression seems to have beneficial effects on metabolic parameters and to protect against HFHS diet effects.

Borderline resectable pancreatic cancer. Challenges and controversies.

Pancreatic cancer is a dismal disease with an increasing incidence. Despite the majority of patients are not candidates for curative surgery, a subgroup of patients classified as borderline resectable pancreatic cancer can be selected in whom a sequential strategy of neoadjuvant therapy followed by surgery can provide better outcomes. Multidisciplinary approach and surgical pancreatic expertise are essential for successfully treating these patients. However, the lack of consensual definitions and therapies make the results of studies very difficult to interpret and hard to be implemented in some settings. In this article, we review the challenges of borderline resectable pancreatic cancer, the complexity of its management and controversies and point out where further research and international cooperation for a consensus strategy is urgently needed.

mRNA expression profiles obtained from microdissected pancreatic cancer cells can predict patient survival.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating malignancies in developed countries because of its very poor prognosis and high mortality rates. By the time PDAC is usually diagnosed only 20-25% of patients are candidates for surgery, and the rate of survival for this cancer is low even when a patient with PDAC does undergo surgery. Lymph node invasion is an extremely bad prognosis factor for this disease. METHODS: We analyzed the mRNA expression profile in 30 PDAC samples from patients with resectable local disease (stages I and II). Neoplastic cells were isolated by laser-microdissection in order to avoid sample 'contamination' by non-tumor cells. Due to important differences in the prognoses of PDAC patients with and without lymph node involvement (stage IIB and stages I-IIA, respectively), we also analyzed the association between the mRNA expression profiles from these groups of patients and their survival. RESULTS: We identified expression profiles associated with patient survival in the whole patient cohort and in each group (stage IIB samples or stage I-IIA samples). Our results indicate that survival-associated genes are different in the groups with and without affected lymph nodes. Survival curves indicate that these expression profiles can help physicians to improve the prognostic classification of patients based on these profiles.

[P16(INK4alpha)/Ki-67 immunocytochemical dual staining for detection of cervical lesions associated to papillomavirus infection]. / Tinción dual inmunocitoquímica de p16)INKalpha/Ki-67 para la detección de lesiones del cuello uterino asociadas a infección por el virus del papiloma humano.

We aimed to explore the expression pattern of p16(INK4alpha)/Ki-67 immunocytochemical dual-staining and to establish the potential clinical utility for early detection of cervical lesions. Liquid-based cytologies of cervical specimens of cervical cancer screening were processed for p16(INK4alpha)/Ki-67 immunocytochemical dual-staining using the CINtec Plus Kit. HPV testing was performed with the INNO-LiPA HPV genotyping Extra Reverse Hybridization Line Probe Assay kit. One hundred and fifteen cervical cytologies were analyzed with the following results: 11(9.6%) were negative for intraepithelial lesions or malignancy (NILM); 32 (27.8%) presented atypical squamous cells of undetermined significance (ASC-US); 62 (53.9%) exhibited low grade squamous intraepithelial lesions (LSIL) and 10 (8.7%) showed high grade squamous intraepithelial lesions (HSIL). No cases of cervical cancer were detected. The overall prevalence of DNA HPV detection was 81.7% (94/115). The following specific HPV genotypes were identified in 42 (45.0%) cases: HPV16 (26.2%), HPV51 (21.4%), HPV52 (14.3%) and HPV66 (7.1%). Viral sequences of an unknown single HPV were detected in 23.8% of the cases. A total of 42/115 (36.5%) were p16(IVK4alpha)/Ki-67 dual-staining-positive, being more frequent in HSIL (70.0%), decreasing in LSIL (44.0%), detected in a minority of ASC-US (25.0%) and negative in NILM cases (p < 0.001). 40/115 cases (34.8%) were positive for both oncogenic HPV and p16(INK4alpha)/Ki-67 dual-staining, including 6/32 (18.8%) ASC-US, 26/62 (42.0%) LSIL and 8/10 (80.0%) HSIL, which represent a strong association between positivity for HPV, p16(INK4alpha)/Ki-67 staining and severe cytological abnormalities (p < 0.001). This methodology could be used to detect unnoticed cervical lesions.

Pathology handling of pancreatoduodenectomy specimens: Approaches and controversies.

Pancreatic cancer, with a 5% 5-year survival rate, is the fourth leading cause of cancer death in Western countries. Unfortunately, only 20% of all patients benefit from surgical treatment. The need to prolong survival has prompted pathologists to develop improved protocols to evaluate pancreatic specimens and their surgical margins. Hopefully, the new protocols will provide clinicians with more powerful prognostic indicators and accurate information to guide their therapeutic decisions. Despite the availability of several guidelines for the handling and pathology reporting of duodenopancreatectomy specimens and their continual updating by expert pathologists, there is no consensus on basic issues such as surgical margins or the definition of incomplete excision (R1) of pancreatic ductal adenocarcinoma. This article reviews the problems and controversies that dealing with duodenopancreatectomy specimens pose to pathologists, the various terms used to define resection margins or infiltration, and reports. After reviewing the literature, including previous guidelines and based on our own experience, we present our protocol for the pathology handling of duodenopancreatectomy specimens.

Tinción dual inmunocitoquímica de p16INKa/Ki-67 para la detección de lesiones del cuello uterino asociadas a infección por el virus del papiloma humano / p16INK4a/Ki-67 immunocytochemical dual staining for detection of cervical lesions associated to papillomavirus infection

Este estudio se llevó a cabo para examinar el patrón de inmunoexpresión simultánea de p16INK4a/Ki-67y establecer su posible utilidad clínica para la detección precoz del cáncer de cuello uterino. Las muestras celulares de cuello uterino fueron seleccionadas de la pesquisa de rutina de cáncer cervical. La detección inmunocitoquímica de p16INK4a/Ki-67se realizó con el kit de trabajo CINtec® Plus. Todos los casos tenían una prueba de virus papiloma humano (VPH). Ciento quince muestras citológicas fueron incluidas: 11(9,6%) fueron negativas para lesión intraepitelial o malignidad (NILM), 32(27,8%) presentaron células escamosas con atipias de significado indeterminado (ASC-US), 62(53,9%) mostraron lesión intraepitelial escamosa de bajo grado (LSIL) y 10(8,7%) lesión intraepitelial escamosa de alto grado (HSIL). La prevalencia general de infección por VPH fue de 81,7% (94/115). En 42 casos (45,0%) se identificaron los siguientes genotipos específicos de VPH: VPH16 (26,2%), VPH51 (21,4%), VPH52 (14,3%) y el genotipo VPH66 (7,1%). De 115 muestras celulares, 42(36,5%) fueron positivas para la tinción dual de p16INK4a/Ki-67, siendo ésta muy frecuente en las muestras citológicas con HSIL (70,0%), disminuyendo en las LSIL (44,0%) y existiendo inmunopositividad en una minoría de ASC-US (25,0%). Ningún caso NILM mostró inmunopositividad para p1(6INK4a)/Ki-67 (p<0,001). En 40/115 casos (34,8%) hubo positividad tanto para infección por VPH oncogénico como para la tinción dual p16INK4a/Ki-67, incluyendo 6/32 (18,8%) con ASC-US, 26/62 (42,0%) con LSIL and 8/10 (80,0%) con HSIL. Esta metodología podría ser utilizada para detectar lesiones en cuello uterino que aún no han sido diagnosticadas o han pasado inadvertidas.

We aimed to explore the expression pattern of p16INK4a/Ki-67 immunocytochemical dual-staining and to establish the potential clinical utility for early detection of cervical lesions. Liquid-based cytologies of cervical specimens of cervical cancer screening were processed for p16INK4a/Ki-67 immunocytochemical dual-staining using the CINtec® Plus Kit. HPV testing was performed with the INNO-LiPA HPV genotyping Extra Reverse Hybridization Line Probe Assay kit. One hundred and fifteen cervical cytologies were analyzed with the following results: 11(9.6%) were negative for intraepithelial lesions or malignancy (NILM); 32(27.8%) presented atypical squamous cells of undetermined significance (ASC-US); 62(53.9%) exhibited low grade squamous intraepithelial lesions (LSIL) and 10(8.7%) showed high grade squamous intraepithelial lesions (HSIL). No cases of cervical cancer were detected. The overall prevalence of DNA HPV detection was 81.7% (94/115). The following specific HPV genotypes were identified in 42 (45.0%) cases: HPV16 (26.2%), HPV51 (21.4%), HPV52 (14.3%) and HPV66 (7.1%). Viral sequences of an unknown single HPV were detected in 23.8%of the cases. A total of 42/115 (36.5%) were p16INK4a/Ki-67 dual-staining-positive, being more frequent in HSIL (70.0%), decreasing in LSIL (44.0%), detected in a minority of ASC-US (25.0%) and negative in NILM cases (p<0.001). 40/115 cases (34.8%) were positive for both oncogenic HPV and p16INK4a/Ki-67 dual-staining, including 6/32 (18.8%) ASC-US, 26/62 (42.0%) LSIL and 8/10 (80.0%) HSIL, which represent a strong association between positivity for HPV, p16INK4a/Ki-67 staining and severe cytological abnormalities (p<0.001). This methodology could be used to detect unnoticed cervical lesions.

Hepatocolangiocarcinoma combinado. Claves para su diagnóstico anatomopatológico / Keys to the histopathological diagnosis of combined hepatocellular-cholangiocarcinoma

El hepatocolangiocarcinoma combinado (HCC) es un tumor primario hepático poco frecuente. Se caracteriza por mostrar elementos inequívocos tanto de hepatocarcinoma (HC) como de colangiocarcinoma (CC), íntimamente relacionados entre sí. Presentamos 2 casos clínicos recientes, en los que el diagnóstico preoperatorio fue de CC en el caso 1 y de HC en el caso 2. Tras la resección quirúrgica el estudio histológico en ambos casos mostró un doble componente de hepatocarcinoma y colangiocarcinoma. Además, en el caso 2 existían áreas donde las células se hacían más indiferenciadas y expresaban marcadores de célula madre. La clasificación histológica de este tipo de tumores ha estado sometida a revisión recientemente y sería conveniente disponer de unas claves diagnósticas anatomopatológicas. En el presente trabajo se realiza una revisión de la literatura y se analizan lo que se consideran claves diagnósticas(AU)

Combined hepatocellular-cholangiocarcinoma is a rare primary hepatic tumour, characterized by unmistakable, intimately mixed elements of both hepatocellular carcinoma and cholangiocarcinoma. We report 2 cases in which the preoperative diagnosis was cholangiocarcinoma (case 1) and hepatocellular carcinoma (case 2). However, the microscopy of the surgical specimen revealed components of typical hepatocellular carcinoma as well as cholangiocarcinoma in both cases. Moreover, case 2 showed areas of undifferentiated cells expressing stem cell markers. As the classification of these tumours has recently changed, histopathological keys for their correct diagnosis would prove helpful. To this end, we have reviewed the pertinent literature in search of such diagnostic aids(AU)

Actinomicosis pulmonar: Diagnóstico por punción-aspiración con aguja fina / Pulmonary actinomycosis: Fine needle aspiration diagnostic

Se presentan 4 casos de actinomicosis pulmonar en pacientes mayores de 40 años, 2 de ellos con enfermedad pulmonar obstructiva crónica (EPOC), que mostraron un aumento de la tos productiva, episodios de disnea, hemoptisis y fiebre de larga evolución. En las radiografías de tórax de rutina se observaban imágenes segmentarias de consolidación aérea, sugestivas de cuadros neumónicos no resueltos o neoplasia. La tomografía axial computarizada (TAC) mostró hallazgos similares a los anteriores. Los cultivos de esputo y las pruebas de Mantoux fueron repetidamente negativos. Debido a la mala evolución de los pacientes y a los hallazgos radiológicos, se practicó una punción-aspiración con aguja fina (PAAF) para descartar neoplasia. En la citología se observaron conglomerados tridimensionales, de bordes filamentosos y aspecto algodonoso compatibles con Actinomyces. El tratamiento antibiótico produjo la mejoría del cuadro clínico y el seguimiento demostró la desaparición de las opacidades radiológicas. Actualmente, la actinomicosis pulmonar es infrecuente y la sintomatología inespecífica, por lo que puede confundirse con procesos neoplásicos. Por tanto, en pacientes con factores de riesgo, síntomas de neumonía subaguda e imágenes radiológicas de consolidación del parénquima es aconsejable considerar la posibilidad de actinomicosis pulmonar. Es una enfermedad tratable y su correcto diagnóstico mediante la PAAF evita al paciente pruebas diagnósticas más agresivas, retrasos en el diagnóstico y le permite una cura completa con tratamiento antibiótico.

We present four cases of pulmonary actinomycosis in patients over 40 years of age, two of them with chronic obstructive pulmonary disease (COPD), showing an increase in productive cough, episodes of dyspnea, hemoptysis and long-term fever. Routine chest radiographs revealed segmental air-space consolidation, suggestive of unresolved pneumonia or neoplasm. Computed tomography (CT) scan showed similar findings to the ones previously described. Sputum cultures for mycobacteriae and Mantoux tests were constantly negative. Due to the poor clinical and radiodological outcome of the patients, a fine needle aspiration (FNA) was made to rule out a neoplasm. Tridimensional filamentous colonies of Actinomyces were observed in cytology. Antibiotic treatment resulted in an improvement of symptoms. The follow-up showed a decrease of the consolidation areas. Pulmonary actinomycosis is rare nowadays and clinical symptoms are unspecific and can be confused with a neoplasm process. Therefore, in patients with risk factors, symptoms of subacute pneumonia and radiologic findings of consolidation, it is advisable to consider pulmonary actinomycosis as a diagnostic possibility. It is a treatable disease and its correct diagnosis by FNA, avoids performing invasive diagnostic tests, delays in the diagnosis and allows for a complete cure by antibiotic therapy.

Foregut cystic malformations in the pancreas. Are definitions clearly established?

CONTEXT: Foregut cystic malformations are common lesions in the mediastinum but are rarely found in subdiaphragmatic locations. Only a few cases have been described within the pancreas where they can easily be misdiagnosed as cystic neoplasms. CASE REPORT: We herein present the case of a 37-year-old female with acute cholangitis in whom a diagnostic work-up revealed a 1 cm solid-cystic heterogeneous lesion located at the head of the pancreas. The patient underwent a pancreaticoduodenectomy. Pathological evaluation demonstrated a cystic cavity lined by pseudostratified tall columnar ciliated epithelium with goblet cells, but lacking cartilage or smooth muscle bundles. Thus, the final diagnosis of the lesion was a ciliated foregut cyst of the pancreas. CONCLUSIONS: A review of the cases published regarding these lesions shows great variability in the taxonomy and a lack of accuracy in the definitions of each different subtype. An easy to use algorithm for the diagnosis of foregut cystic malformations subtypes, based on epithelial lining and wall features, is presented.

[Detection of human papilloma virus (HPV) in liquid-based cervical samples. Correlation with protein p16INK4a expression]. / Detección de virus papiloma humano (HPV) a partir de muestras celulares de cuello uterino en base liquida. Correlación con la inmunorreactividad de la proteina p 16INK4a.

The liquid-based cervical cytology improves the quality of the sample and the residual sample could be used efficiently to carry out complementary tests, such as the detection of HPV DNA and the immunocytochemical biomarkers study. The purpose of this study was to correlate the presence of HPV and immunoexpression of p16INK4a in liquid-based cervical samples to examine the utility of these new tools in the detection of cervical cancer. The included patients (n = 67) presented an abnormal cytology or previous cervical pathology. The HPV detection and genotyping were carried out with PCR-SPF10/LiPA (INNOLiPA Extra Amp) and for p16INK4a immunodetection was used antibody clone E6H4. The conventional cytology provided the same cytologic interpretations that those of liquid-based cytology. The overall HPV prevalence was 43.3% (29/67). HPV16 was the most frequent viral type (31.03%) and 48.3% of the cases were infected with multiple HPV types. p16INK4a immunoexpression was observed in 35.8% of liquid-based cytological samples and this was significantly (p < 0.020) associated to the HPV presence. These results support the evidence that the implementation of new technologies in the daily routine of the laboratory, contribute significantly in the early detection of cervical cancer and provide important data to help in the patient's efficient management. The combined use of HPV detection and p16INK4a expression could be used for evaluation of patients with more risk to develop significant cervical lesions.

Detección de virus papiloma humano (HPV) a partir de muestras celulares de cuello uterino en base líquida: Correlación con la inmunorreactividad de la proteína p16INK4a / Detection of human papilloma virus (HPV) in liquid-based cervical samples: Correlation with protein p16INK4a expression

La citología del cuello uterino en base líquida mejora la calidad de la muestra y el material residual podría ser utilizado para realizar pruebas complementarias, como la detección del virus papiloma humano (HPV) y estudio inmunocitoquímico de biomarcadores. El propósito de este estudio fue correlacionar la presencia de HPV y la inmunoexpresión de p16INK4a en las muestras citológicas en base líquida para examinar la utilidad de estas nuevas herramientas en la detección de cáncer de cuello uterino. Las pacientes incluidas (n=67) presentaban una citología anormal o patología cervical previa. La detección y genotipificación de HPV se realizó con PCR-SPF10/LiPA (INNOLiPA Extra Amp) y para la inmunodetección de p16INK4a se utilizó el anticuerpo clon E6H4. La citología convencional proporcionó los mismos hallazgos citológicos que la citología en base líquida. La prevalencia general del HPV fue de 43,3% (29/67). El HPV16 fue el tipo viral mas frecuente (31,03%) y el 48,3% de los casos presentó infección múltiple. En el 35,8% de las muestras cervicales se detectó inmunoexpresión de la p16INK4a y ésta fue significativamente (p<0,020) asociada a la presencia de HPV. Estos resultados apoyan la evidencia que la implementación de nuevas tecnologías en la rutina diaria del laboratorio contribuye significativamente en la detección precoz del cáncer de cuello uterino y en el aporte de datos importantes para facilitar en el manejo clínico adecuado de la paciente. La detección de HPV combinada con la p16INK4a podría ser utilizado en la evaluación de pacientes con mayor riesgo a desarrollar lesiones cervicales significativas.

The liquid-based cervical cytology improves the quality of the sample and the residual sample could be used efficiently to carry out complementary tests, such as the detection of HPV DNA and the immunocytochemical biomarkers study. The purpose of this study was to correlate the presence of HPV and immunoexpression of p16INK4a in liquid-based cervical samples to examine the utility of these new tools in the detection of cervical cancer. The included patients (n=67) presented an abnormal cytology or previous cervical pathology. The HPV detection and genotyping were carried out with PCR-SPF10/LiPA (INNOLiPA Extra Amp) and for p16INK4a immunodetection was used antibody clone E6H4. The conventional cytology provided the same cytologic interpretations that those of liquid-based cytology. The overall HPV prevalence was 43.3% (29/67). HPV16 was the most frequent viral type (31.03%) and 48.3% of the cases were infected with multiple HPV types. p16INK4a immunoexpression was observed in 35.8% of liquid-based cytological samples and this was significantly (p < 0.020) associated to the HPV presence. These results support the evidence that the implementation of new technologies in the daily routine of the laboratory, contribute significantly in the early detection of cervical cancer and provide important data to help in the patient’s efficient management. The combined use of HPV detection and p16INK4a expression could be used for evaluation of patients with more risk to develop significant cervical lesions.

[Pulmonary actinomycosis. Fine needle aspiration diagnostic]. / Actinomicosis pulmonar. Diagnóstico por punción-aspiración con aguja fina.

We present four cases of pulmonary actinomycosis in patients over 40 years of age, two of them with chronic obstructive pulmonary disease (COPD), showing an increase in productive cough, episodes of dyspnea, hemoptysis and long-term fever. Routine chest radiographs revealed segmental air-space consolidation, suggestive of unresolved pneumonia or neoplasm. Computed tomography (CT) scan showed similar findings to the ones previously described. Sputum cultures for mycobacteriae and Mantoux tests were constantly negative. Due to the poor clinical and radiodological outcome of the patients, a fine needle aspiration (FNA) was made to rule out a neoplasm. Tridimensional filamentous colonies of Actinomyces were observed in cytology. Antibiotic treatment resulted in an improvement of symptoms. The follow-up showed a decrease of the consolidation areas. Pulmonary actinomycosis is rare nowadays and clinical symptoms are unspecific and can be confused with a neoplasm process. Therefore, in patients with risk factors, symptoms of subacute pneumonia and radiologic findings of consolidation, it is advisable to consider pulmonary actinomycosis as a diagnostic possibility. It is a treatable disease and its correct diagnosis by FNA, avoids performing invasive diagnostic tests, delays in the diagnosis and allows for a complete cure by antibiotic therapy.

Protocolo de tallado, estudio e informe anatomopatológico de las piezas de duodenopancreatectomía cefálica por carcinoma de páncreas / The protocol for the macroscopy, sampling and reporting of surgical specimens from pancreatoduodenectomy for carcinoma of the pancreas

El cáncer de páncreas representa la cuarta causa de muerte por cáncer en los países desarrollados. El creciente interés por parte de cirujanos y oncólogos de mejorar las tasas de supervivencia ha incidido directamente en los laboratorios de anatomía patológica, exigiendo de los mismos una estandarización en el tallado y valoración de los márgenes de resección. En el presente trabajo analizaremos los problemas anatómicos de las piezas de duodenopancreatectomía cefálica y revisaremos las distintas nomenclaturas utilizadas para definir los diferentes márgenes de resección, así como su afectación. Finalmente presentamos el protocolo de tallado y evaluación que utilizamos en el Hospital Clínico Universitario de Valencia, basado en trabajos previos de patólogos europeos y americanos, así como en nuestra propia experiencia(AU)

Cancer of the pancreas is the fourth cause of death due to cancer in developed countries and surgeons and oncologists are showing an increasing interest in the improvement of survival. This has prompted pathologists to develop better, standardized protocols for the evaluation of surgical specimens from pancreatectomies. The different problems that the pathologist may encounter when examining surgical specimens from pancreatoduodenectomies, as well as the different nomenclature used to define resection margins and infiltration are discussed. The protocol followed at the University Hospital of Valencia, based on European and American protocols as well as our own experience, is described(AU)

Evaluación de la calidad de los diagnósticos premortem de causas de muerte en las autopsias del Hospital Clínico Universitario de Valencia (1985-1992) / A comparative study of the pre- and post-mortem diagnoses of the cause of death in the University Hospital of Valencia between 1985 and 1992

Se estudiaron 998 autopsias realizadas en el Servicio deAnatomía Patológica del Hospital Clínico Universitario deValencia entre 1985 y 1992, introducidas y procesadas en elSistema Automatizado de Registro y Control de AnatomíaPatológica (SARCAP) en el Hospital «Hermanos Ameijeiras» de La Habana, Cuba. Los principales resultados fueron:predominio del sexo masculino y las edades avanzadas; lasprincipales causas básicas de muerte fueron los tumoresmalignos, la ateromatosis coronaria, la cirrosis hepática y elSIDA, y las principales causas directas de muerte fueron labronconeumonía, la extensión del cáncer y el tromboembolismopulmonar. Hubo 10,6% de discrepancias diagnósticaspremortem y postmortem en la Causa Básica de Muerte(CBM) y 30,7% en la Causa Directa de Muerte (CDM). Sedestaca la importancia del estudio multicausal de la muertey la utilidad del SARCAP para la creación de una base dedatos de todas autopsias realizadas en el Hospital Universitariode Valencia y que forme parte de una base de datos detodas las autopsias Iberoamericana(AU)

998 necropsies carried out in the Department of Pathologyof the University Hospital of Valencia between 1985and 1992 were evaluated and the data obtained was analyzedby the Pathology Registry and Automated ControlSystem (PRACS) at the «Hermanos Ameijeiras» Hospital inLa Habana (Cuba). The results showed a predominance ofelderly males and that the principal, basic causes of death(BCD) were malignant tumours, coronary atheromatosis,hepatic cirrhosis and AIDS. The major direct causes ofdeath (DCD) were broncopneumonia, tumour progressionand thromboembolism in the lung. A 10.6% discrepancywas found between the pre- and post-mortem results ofBCD and a 30.7% discrepancy in the results of DCD. It wasconcluded that a multicausal study of death is important andthat the PRACS is a useful tool for creating a common databaseof all the necropsies performed in the University Hospitalof Valencia within an Iberoamerican network(AU)