Correlation of liver fibrosis quantification by morphometry using HepaScan with the analysis of liver biopsies. A pilot study.

BACKGROUND: The gold standard for determining the degree of liver fibrosis (LF) continues to be biopsy evaluation. There are morphometry techniques that allow LF to be quantified on histopathological studies. OBJECTIVE: To measure the correlation between LF histological evaluation and fibrosis percentage (FP) morphometric quantification using the HepaScan software. MATERIAL AND METHODS: Observational, analytical, cross-sectional, prospective, prolective pilot study in which liver histological sections from 29 people who died from some liver disease and from 22 people who died from other causes (controls) were analyzed. FP was calculated with HepaScan on digital photographs of histological sections stained with the Masson technique, comparing it with the diagnosis established by three expert pathologists. RESULTS: Four-hundred and one images from the group with liver disease and 250 from the control group were analyzed. Inter-observer agreement had a kappa index of 0.329. There were FP statistically significant differences (p = 0.0001) between histopathological classification groups. HepaScan predictive capacity based on the area under the receiver operating characteristic curve was 0.983, 0.812, and 0.895 for mild, moderate, and severe fibrosis, respectively. CONCLUSIONS: HepaScan showed very good performance for evaluating FP in histological sections, which is why it can contribute to qualitative pathological diagnosis.

ANTECEDENTES: El estándar de oro para determinar el grado de fibrosis hepática (FH) continúa siendo la evaluación de la biopsia. Existen técnicas de morfometría que permiten cuantificar la FH en estudios histopatológicos. OBJETIVO: Medir la correlación entre la evaluación histológica de FH y la cuantificación por morfometría del porcentaje de fibrosis (PF) mediante HepaScan. MATERIAL Y MÉTODOS: Estudio piloto observacional, analítico, transversal, prospectivo y prolectivo en el que se analizaron cortes histopatológicos de hígado de 29 personas fallecidas por alguna hepatopatía y 22 personas fallecidas por otras causas (controles). El PF se calculó con HepaScan en fotografías digitales de cortes histológicos teñidos con la técnica Masson, comparándolo con el diagnóstico de tres patólogos expertos. RESULTADOS: Fueron analizadas 401 imágenes del grupo con hepatopatía y 250 del grupo de control. La concordancia interobservador tuvo un índice kappa de 0.329. Entre los grupos de clasificación histopatológica existieron diferencias estadísticas en el PF (p = 0.0001). La capacidad predictiva de HepaScan con base en el área bajo la curva característica operativa del receptor fue de 0.983, 0.812 y 0.895 para fibrosis leve, moderada y severa, respectivamente. CONCLUSIONES: HepaScan mostró muy buen desempeño para evaluar el PF en cortes histológicos, por lo que puede coadyuvar al diagnóstico patológico cualitativo.

Laparoscopic cholecystectomy: Histopathological analysis of metabolic associated fatty liver disease and fibrosis.

INTRODUCTION: Metabolic (dysfunction) associated fatty liver disease (MAFLD) and cholelithiasis are highly prevalent and are associated with common risk factors such as obesity, hypertriglyceridemia, and fasting glucose levels; however, it is not clear whether cholelithiasis is associated with MAFLD or fibrosis. OBJECTIVE: To determine MAFLD severity and associated risk factors in patients diagnosed with cholelithiasis. MATERIALS AND METHODS: Observational, cross-sectional and prolective study (from October 2018 to March 2020) of patients undergoing elective laparoscopic cholecystectomy with liver biopsy, excluding other causes of hepatic disease or significant alcohol consumption. MAFLD detection was based on histology using the Kleiner score and one of the following criteria: overweight/obesity, T2DM, or evidence of metabolic dysregulation. The AST to Platelet Ratio Index, the NAFLD Fibrosis Score, the fibrosis-4 index and the hepatic steatosis index were performed to assess the relationship of non-invasive hepatic scores with histopathology. RESULTS: 80 patients median age (interquartile range) was 42 (18) years, with a BMI of 27.9 (6.11) Kg/m2. Of all patients, 58.8% had MAFLD, 78.7% were women, and 13.8% had the severe form (formerly named NASH). No substantial correlation between biochemical parameters and histopathological analysis of MAFLD and fibrosis was observed. CONCLUSION: Because cholelithiasis and MAFLD are highly prevalent diseases, it is essential to conduct studies on the relationship between both pathologies. Currently, liver biopsy is the best diagnostic method since the predictive biochemical models did not show a substantial correlation to classify MAFLD. Its early detection is relevant since a considerable percentage of advanced fibrosis (8.7%) was found.

CRHR2/Ucn2 signaling is a novel regulator of miR-7/YY1/Fas circuitry contributing to reversal of colorectal cancer cell resistance to Fas-mediated apoptosis.

Colorectal cancer (CRC) responds poorly to immuno-mediated cytotoxicity. Underexpression of corticotropin-releasing-hormone-receptor-2 (CRHR2) in CRC, promotes tumor survival, growth and Epithelial to Mesenchymal Transition (EMT), in vitro and in vivo. We explored the role of CRHR2 downregulation in CRC cell resistance to Fas/FasL-mediated apoptosis and the underlying molecular mechanism. CRC cell sensitivity to CH11-induced apoptosis was compared between Urocortin-2 (Ucn2)-stimulated parental and CRHR2-overexpressing CRC cell lines and targets of CRHR2/Ucn2 signaling were identified through in vitro and ex vivo analyses. Induced CRHR2/Ucn2 signaling in SW620 and DLD1 cells increased specifically their sensitivity to CH11-mediated apoptosis, via Fas mRNA and protein upregulation. CRC compared to control tissues had reduced Fas expression that was associated with lost CRHR2 mRNA, poor tumor differentiation and high risk for distant metastasis. YY1 silencing increased Fas promoter activity in SW620 and re-sensitized them to CH11-apoptosis, thus suggesting YY1 as a putative transcriptional repressor of Fas in CRC. An inverse correlation between Fas and YY1 expression was confirmed in CRC tissue arrays, while elevated YY1 mRNA was clinically relevant with advanced CRC grade and higher risk for distant metastasis. CRHR2/Ucn2 signaling downregulated specifically YY1 expression through miR-7 elevation, while miR-7 modulation in miR-7high SW620-CRHR2+ and miR-7low HCT116 cells, had opposite effects on YY1 and Fas expressions and cell sensitivity to CH11-killing. CRHR2/Ucn2 signaling is a negative regulator of CRC cell resistance to Fas/FasL-apoptosis via targeting the miR-7/YY1/Fas circuitry. CRHR2 restoration might prove effective in managing CRC response to immune-mediated apoptotic stimuli.

Primary lymphomas of the breast: a report on 5 cases studied in a period of 5 years at the Hospital General de México.

Breast lymphomas can be primary or secondary. Among the primary lymphomas, the most common histologic types are the large B-cell diffuse lymphomas and the extranodal B mucosa-associated lymphatic tissue lymphomas. We studied 5 cases of primary breast lymphoma in female patients. The criteria for the diagnosis were based on the proposal of Wiseman and Liao: (1) in the biopsy or surgical specimen, the lymphoma involves the breast parenchyma, and (2) nonsystemic disease at diagnosis. Clinical data, histologic findings, immunohistochemical reactions, treatment, and clinical follow-up were reviewed. The 5 patients were young women with average age of 27 years; the youngest was 20 years old, and the oldest was 44 years old. The right breast was the most affected, and 1 patient was HIV positive. The most common symptoms were the presence of nodes, progressive increase of volume, collateral venous network, and hemorrhagic discharge from the nipple. The clinical course was of 1 to 14 months before diagnosis. Three patients died because of central nervous system infiltration, one is still alive, and the other was lost during follow-up. Histologically, all primary breast lymphomas were large B-cell lymphomas; one had focal starry sky pattern, and the other 3 were centroblastic. All were positive to CD20 and CD79(a), 3 expressed bcl2, and 2 expressed bcl6. The proliferation index was between 60% and 80%. Primary breast lymphomas are rare. The average age of our patients was 27 years, and their clinical course was aggressive with central nervous system infiltration. The most common histologic type was the large B-cell diffuse lymphoma. Differential diagnosis must be established in the presence of poorly differentiated lobules and ductal carcinoma.

Follicular dendritic cell sarcoma/tumor: 2 cases of a rare tumor of difficult clinical and pathological diagnosis.

The follicular dendritic cell sarcoma/tumor is a neoplasic proliferation of fusiform and ovoid cells with characteristic morphology and immunohistochemical pattern. The sarcoma/tumor term is designated due to the variability of the cytological status and, in many cases, its indeterminate clinical course. This report presents the 2 first cases seen at the Hospital General de México, OD (General Hospital of Mexico). The aim of this study is to contribute to the morphology and immunophenotype of this infrequent neoplasm, as well as discuss its differential diagnosis and clinical evolution.

Regulation of Krüppel-Like Factor 4 (KLF4) expression through the transcription factor Yin-Yang 1 (YY1) in non-Hodgkin B-cell lymphoma.

Krüppel-Like Factor 4 (KLF4) is a member of the KLF transcription factor family, and evidence suggests that KLF4 is either an oncogene or a tumor suppressor. The regulatory mechanism underlying KLF4 expression in cancer, and specifically in lymphoma, is still not understood. Bioinformatics analysis revealed two YY1 putative binding sites in the KLF4 promoter region (-950 bp and -105 bp). Here, the potential regulation of KLF4 by YY1 in NHL was analyzed. Mutation of the putative YY1 binding sites in a previously reported system containing the KLF4 promoter region and CHIP analysis confirmed that these binding sites are important for KLF4 regulation. B-NHL cell lines showed that both KLF4 and YY1 are co-expressed, and transfection with siRNA-YY1 resulted in significant inhibition of KLF4. The clinical implications of YY1 in the transcriptional regulation of KLF4 were investigated by IHC in a TMA with 43 samples of subtypes DLBCL and FL, and all tumor tissues expressing YY1 demonstrated a correlation with KLF4 expression, which was consistent with bioinformatics analyses in several databases. Our findings demonstrated that KLF4 can be transcriptionally regulated by YY1 in B-NHL, and a correlation between YY1 expression and KLF4 was found in clinical samples. Hence, both YY1 and KLF4 may be possible therapeutic biomarkers of NHL.

[Programa de entrenamiento en reparacion vascular en modelo experimental para residentes de cirugía general]. / Vascular reparation training program in experimental model for general surgery residents.

INTRODUCCIÓN: Los programas de entrenamiento simulado permiten optimizar recursos, aumentar la práctica técnica y acortar curvas de aprendizaje, y constituyen un método seguro, estandarizado y validado de aprendizaje para todos los entrenados. OBJETIVO: Desarrollar un programa de entrenamiento vascular mediante la elaboración de una anastomosis término-terminal de un vaso en un modelo experimental para residentes de cirugía general. MÉTODO: Para el desarrollo de este modelo de entrenamiento se utilizó una extremidad amputada a nivel supracondíleo libre de proceso médico-legal. Se realizó la disección de la arteria femoral, se dividió en dos porciones y se realizó una anastomosis término-terminal. Se diseño un sistema que incluye la evaluación de las siguientes variables utlizando la escalas OSATS (Objetive Structured Assesment of Technical Skills) y Likert: 1) nudo manual y punto simple; 2) permeabilidad de la anastomosis; 3) simetría de los puntos; 4) fuga de anastomosis; y 5) tiempo total de anastomosis. DISCUSIÓN: Al reconocer las ventajas del entrenamiento experimental, se propone un modelo biológico experimental reproducible, estandarizado y de bajo costo. CONCLUSIONES: El desarrollo de modelos biológicos experimentales permite al cirujano general la adquisición de habilidades y destrezas quirúrgicas, mejorando el desempeño durante un procedimiento quirúrgico y reduciendo riesgos. INTRODUCTION: Simulated training programs allow to optimize resources, increase technical practice and shorten learning curves, constituting a safe, standardized and validated method of learning for all those trained. OBJECTIVE: Develop a vascular training program through the elaboration of an end to end anastomosis of a vessel in an experimental model for General Surgery residents. METHOD: For the development of this training model, an amputated limb was used at the supracondylar level free of medical-legal process. The dissection of the femoral artery was performed, it was divided into two portions and an end to end anastomosis was performed. A system was designed that included the evaluation of the following variables using the OSATS (Objective Structured Assessment of Technical Skills) and Likert scales: 1) manual knot and single stitch; 2) permeability of the anastomosis; 3) symmetry of the stitches; 4) Anastomosis leakage; and 5) total time of the anastomosis. DISCUSSION: Recognizing the advantages of experimental training, a reproducible, standardized, and low cost experimental biological model is proposed. CONCLUSIONS: The development of experimental biological models, allows the general surgeon the acquisition of surgical skills and abilities, improving performance during a surgical procedure and reducing risks.

Correlación de la cuantificación de fibrosis hepática por morfometría mediante HepaScan con el análisis de las biopsias hepáticas. Estudio piloto / Correlation of liver fibrosis quantification by morphometry using HepaScan with the analysis of liver biopsies. A pilot study

Resumen Antecedentes: El estándar de oro para determinar el grado de fibrosis hepática (FH) continúa siendo la evaluación de la biopsia. Existen técnicas de morfometría que permiten cuantificar la FH en estudios histopatológicos. Objetivo: Medir la correlación entre la evaluación histológica de FH y la cuantificación por morfometría del porcentaje de fibrosis (PF) mediante HepaScan. Material y métodos: Estudio piloto observacional, analítico, transversal, prospectivo y prolectivo en el que se analizaron cortes histopatológicos de hígado de 29 personas fallecidas por alguna hepatopatía y 22 personas fallecidas por otras causas (controles). El PF se calculó con HepaScan en fotografías digitales de cortes histológicos teñidos con la técnica Masson, comparándolo con el diagnóstico de tres patólogos expertos. Resultados: Fueron analizadas 401 imágenes del grupo con hepatopatía y 250 del grupo de control. La concordancia interobservador tuvo un índice kappa de 0.329. Entre los grupos de clasificación histopatológica existieron diferencias estadísticas en el PF (p = 0.0001). La capacidad predictiva de HepaScan con base en el área bajo la curva característica operativa del receptor fue de 0.983, 0.812 y 0.895 para fibrosis leve, moderada y severa, respectivamente. Conclusiones: HepaScan mostró muy buen desempeño para evaluar el PF en cortes histológicos, por lo que puede coadyuvar al diagnóstico patológico cualitativo.

Abstract Background: The gold standard for determining the degree of liver fibrosis (LF) continues to be biopsy evaluation. There are morphometry techniques that allow LF to be quantified on histopathological studies. Objective: To measure the correlation between LF histological evaluation and fibrosis percentage (FP) morphometric quantification using the HepaScan software. Material and methods: Observational, analytical, cross-sectional, prospective, prolective pilot study in which liver histological sections from 29 people who died from some liver disease and from 22 people who died from other causes (controls) were analyzed. FP was calculated with HepaScan on digital photographs of histological sections stained with the Masson technique, comparing it with the diagnosis established by three expert pathologists. Results: Four-hundred and one images from the group with liver disease and 250 from the control group were analyzed. Inter-observer agreement had a kappa index of 0.329. There were FP statistically significant differences (p = 0.0001) between histopathological classification groups. HepaScan predictive capacity based on the area under the receiver operating characteristic curve was 0.983, 0.812, and 0.895 for mild, moderate, and severe fibrosis, respectively. Conclusions: HepaScan showed very good performance for evaluating FP in histological sections, which is why it can contribute to qualitative pathological diagnosis.

Dual role of hypoxia-inducible factor 1 α in experimental pulmonary tuberculosis: its implication as a new therapeutic target.

AIM: Investigate the role of hypoxia-inducible factor-1α (HIF-1α) in pulmonary tuberculosis (TB). METHODS & RESULTS: A model of progressive pulmonary TB in BALB/c mice, immunohistochemistry and digital pathology were used. High HIF-1α expression was observed during early TB in activated macrophages. During late TB, even higher HIF-1α expression was observed in foamy macrophages, which are resistant to apoptosis. Blocking HIF-1α during early infection with 2-methoxyestradiol worsened the disease, while during late TB, it induced macrophage apoptosis and decreased bacillary loads. CONCLUSION: HIF-1α has a dual role in experimental TB. This finding could have therapeutic implications because combined treatment with 2-methoxyestradiol and antibiotics appeared to eliminate mycobacteria more efficiently than conventional chemotherapy during advanced disease.

Fluorescence Spectroscopy as a Tool for the Assessment of Liver Samples with Several Stages of Fibrosis.

BACKGROUND: During the last years, fluorescence spectroscopy has been used as a potential tool for the evaluation and characterization of tissues with different disease conditions due to its low cost, high sensitivity, and minimally or noninvasive character. OBJECTIVE: In this study, fluorescence spectroscopy was used to study 19 paraffin blocks containing human liver tissue from biopsies. METHODS AND RESULTS: All samples were previously analyzed by two senior pathologists in a single-blind trial. After their evaluation, four liver samples were classified as nonfibrosis (F0), four as initial fibrosis (F1-F2), four as advanced fibrosis (F3), and six as cirrhosis (F4). The fluorescence was induced at different wavelengths as follows: 330, 365, and 405 nm using a portable fiber-optic system. The fluorescence spectra were recorded in the range of 400-750 nm. A distinctive correlation between the shape of each spectrum and the level of fibrosis in the liver sample was detected. A multi-variate statistical analysis based on principal component analysis followed by linear discrimination analysis was applied to develop algorithms able to distinguish different stages of fibrosis based on the characteristics of fluorescence spectra. Pairwise comparisons were performed: F0 versus F1-F2, F1-F2 versus F3, F3 versus F4, and F1-F2 versus F4. The algorithms applied to each set of data yielded values of sensitivity and specificity that were higher than 90% and 95%, respectively, in all the analyzed cases. CONCLUSIONS: With this study, it is concluded that fluorescence spectroscopy can be used as a complementary tool for the assessment of liver fibrosis in liver tissue samples, which sets the stage for subsequent clinical trials.

Mediastinal pleomorphic liposarcoma diagnosed by fine needle aspiration biopsy: a case report.

BACKGROUND: Progress in radiology and pathology for diagnosing mediastinal tumors has R been made in recent decades, thanks to the use of fine needle aspiration biopsy (FNAB) guided by computed tomography, which has replaced mediastinoscopy and open biopsies. CASE: A 66-year-old male had a history o productive coughing with mucopurulent expectoration, progressive dyspnea, arthralgias, myalgias, astenia and adynamia for the previous 3 months. A CT scan and magnetic resonance imaging revealed a poorly limited tumor mass ofheterogeneous den sity in the anterior mediastinum. FNAB of the tumor mass showed malignant cells compatible with liposarcoma. CONCLUSLON: Of the several types of mesenchymal mediastinal neoplasms, liposarcoma is the most important. Many of them are seen in adults, and <10 cases have been diagnosed in children. The symptoms are related to compression of the nearby airways. Usually liposarcomas are yellow, lobed tumors without capsules that infiltrate adjacent organs and tissues. Microscopically, they have the same histologic spectrum as tumors originating in other sites. Thus, it is common to observe all the histologic varieties of soft tissue liposarcomas. The identification of lipoblasts is the key to the correct diagnosis in FNAB material.

A novel role of Yin-Yang-1 in pulmonary tuberculosis through the regulation of the chemokine CCL4.

Mycobacterium tuberculosis (M. tb) is the etiological agent of pulmonary tuberculosis (TB); this disease remains a worldwide health problem. Yin-Yang-1 (YY1) plays a major role in the maintenance and progression of some pulmonary diseases, including pulmonary fibrosis. However, the role of YY1 in TB remains unknown. The aim of this study was to elucidate the role of YY1 in the regulation of CCL4 and its implication in TB. We determined whether YY1 regulates CCL4 using reporter plasmids, ChIP and siRNA assays. Immunohistochemistry and digital pathology were used to measure the expression of YY1 and CCL4 in a mouse model of TB. A retrospective comparison of patients with TB and control subjects was used to measure the expression of YY1 and CCL4 using tissue microarrays. Our results showed that YY1 regulates the transcription of CCL4; moreover, YY1, CCL4 and TGF-ß were overexpressed in the lung tissues of mice with TB during the late stages of the disease and the tissues of TB patients. The expression of CCL4 and TGF-ß correlated with YY1 expression. In conclusion, YY1 regulates CCL4 transcription; moreover, YY1 is overexpressed in experimental and human TB and is positively correlated with CCL4 and TGF-ß expression. Therefore, treatments that decrease YY1 expression may be a new therapeutic strategy against TB.

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

BACKGROUND: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. METHODS: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. RESULTS: A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. CONCLUSIONS: HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs.

Diagnosis of thymolipoma with fine needle aspiration biopsy. Report of a case initially misdiagnosed as liposarcoma.

BACKGROUND: Thymolipomas are the most outstanding mesenchymal mediastinal tumors although they represent only a small percentage of thymic neoplasms. Their histogenesis remains unsolved, and they are usually benign. Fine needle aspiration biopsy (FNAB) has become the method of choice for the study of mediastinal tumors, including thymolipomas. Making the correct diagnosis depends on the availability of all thymic and lipomatous components as well as on the correct application of a differential diagnosis with other lipomatous tumors. CASE: A 24-year-old woman had a 3-month history of coughing with sputum, fever, asthenia, adynamia, headaches and anemia. Physical examination revealed a bilateral pulmonary condensation syndrome. Imaging studies showed a well-defined, large mass occupying both hemithoraxes and the mediastinum. FNAB revealed an admixture of atypical adipocytes, nonneoplasic lymphoid tissue and capillaries with prominent endothelium. An initial diagnosis of well-differentiated liposarcoma was made. A 2.8-kg, encapsulated, yellowish gray mediastinal tumor was surgically removed. Mature adipose tissue intermingled with abundant thymic tissue containing numerous Hassall's corpuscles were seen histologically. Immunohistochemical markers for thymic epithelium, lymphoid tissue and adipocytes were all positive. Thymolipoma was the final diagnosis. The anemia subsided with resection of the tumor, and the patient was disease free 2.5 years after surgery. CONCLUSION: To the best of our knowledge, this is the second report of a thymolipoma studied with FNAB. The criteria for the differential diagnosis between thymolipomas and other lipomatous tumours should be kept in mind.

Diffuse reflectance spectroscopy as a possible tool to complement liver biopsy for grading hepatic fibrosis in paraffin-preserved human liver specimens.

A diffuse reflectance spectroscopy-based method to score fibrosis in paraffin-preserved human liver specimens has been developed and is reported here. Paraffin blocks containing human liver tissue were collected from the General Hospital of Mexico and included in the study with the patients' written consent. The score of liver fibrosis was determined in each sample by two experienced pathologists in a single-blind fashion. Spectral measurements were acquired at 450-750 nm by establishing surface contact between the optical probe and the preserved tissue. According to the histological evaluation, four liver samples showed no evidence of fibrosis and were categorized as F0, four hepatic specimens exhibited an initial degree of fibrosis (F1-F2), five liver specimens showed a severe degree of fibrosis (F3), and six samples exhibited cirrhosis (F4). The human liver tissue showed a characteristic diffuse reflectance spectrum associated with the progressive stages of fibrosis. In the F0 liver samples, the diffuse reflection intensity gradually increased in the wavelength range of 450-750 nm. In contrast, the F1-F2, F3, and F4 specimens showed corresponding 1.5-, 2-, and 5.5-fold decreases in the intensity of diffuse reflectance compared to the F0 liver specimens. At 650 nm, all the stages of liver fibrosis were clearly distinguished from each other with high sensitivity and specificity (92-100%). To our knowledge, this is the first study reporting a distinctive diffuse reflectance spectrum for each stage of fibrosis in paraffin-preserved human liver specimens. These results suggest that diffuse reflectance spectroscopy may represent a complementary tool to liver biopsy for grading fibrosis.

Abdominal wall defects: autopsy findings of distinct groups suggest different pathogenetic mechanisms.

Central and lateral abdominal wall defects are probably distinct and likely arise from different pathogenetic mechanisms. An autopsy study was done using data from a total of 45 central and lateral abdominal wall defect cases to evaluate if they are indeed separate entities and to suggest possible mechanisms involved in their formation. Central defects were found to be statistically different from lateral defects; malformations that co-existed with central defects were mainly bilateral and internal and also involved "inferior" organs in relation to fetal-embryonal blood flow. Patients with lateral defects were more often female, and their coexistent defects were usually unilateral and external, with only 1 defect occurring in an "inferior" organ. These results indicate mechanisms of a vascular perfusion deficit for the majority of the central defects and of external disruption for the lateral defects.

Detección del virus del papiloma humano en la neoplasia escamosa de la superficie ocular por histopatología y estudio molecular / Detection of human papilloma virus in ocular surface squamous neoplasia by histopathology and molecular methods

Identificar la presencia del virus del papiloma humano (HPV, por su sigla en inglés) genotipos16 y 18 en la neoplasia escamosa de la superficie ocular (NESO) y la coilocitosis, que es el dato histopatológico en infecciones por este virus. Métodos: Se estudiaron 35 muestras en parafina de NESO en busca de infección por HPV por histopatología, reacción en cadena de la polimerasa (PCR) y secuenciación. Resultados: No se encontraron cambios histopatológicos característicos de la infección por HPV (coilocitosis). El ADN del HPV fue detectado en 13 de las 26 muestras (50%) que amplificaron betaglobina. Las 13 muestras fueron negativas para HPV 18 y positivas para HPV 16, en dos muestras además se identificó el genotipo 59 y en una, el genotipo 35 por secuenciación. Tres muestras presentaron doble infección, una por HPV16 y 35, y dos por HPV16 y 59. Conclusiones: En este estudio mostramos una relación significativa de la NESO con el HPV; el genotipo 16 fue el más común. También se presentaron infecciones dobles por los genotipos 35 y 59. La PCR es una prueba de mayor sensibilidad que el estudio histopatológico para la detección del HPV...

Convergencia de los síndromes Vacter-H y Prune Belly / Convergence of the Vacter-H and Prune Belly syndromes

Se informa el caso clinicopatológico de un niño pretérmino que presentó anomalías de los síndromes prune belly y VACTERL con hidrocefalia sin antecedentes consanguíneos. En la autopsia se encontró facies de Potter, orejas de implantación baja y microtia, abdomen prominente, arteria umbilical única. El corazón presentó canal auriculoventricular común, tronco arterial común, foramen oval abierto, pulmón derecho unilobular y el derecho trilobular. El intestino delgado mostró divertículo de Meckel. Había malformación anorrectal alta. Los riñones tenían enfermedad glomeruloquística, dilatación de cálices y pelvis renal, los ureteros estaban dilatados con presencia de una valva en el uretero izquierdo, la vejiga estaba aumentada de tamaño y dilatación del uraco, hipoplasia de la próstata y estenosis de la uretra, criptorquidia bilateral, displasia y alteración del número de vértebras y craneosinostosis. Había hidrocefalia y agenesia del septum pellucidum. Las alteraciones que originaron obstrucción urinaria pudieron ser producidas en etapas tempranas del desarrollo embrionario coincidiendo anomalías del síndrome VACTERL-H y prune belly. En la literatura revisada no encontramos una descripción semejante.

La variante letal del síndrome Prune Belly: informe de dos casos / The lethal variant of the \"Prune Belly's\" syndrome: two cases report

En este informe se describen dos casos de la variante letal del síndrome de Prune Belly en que la obstrucción de la uretra produjo graves alteraciones del sistema urinario con distensión vesical y ureteral con repercusión secundaria en la pared abdominal y daño renal bilateral por displasia. Se comenta la etiopatogenia de este síndrome de acuerdo a la teoría embriológica del mesodermo, así como de la teoría de la secuencia de la obstrucción uretral en las etapas tempranas del desarrollo que repercuten en la pared abdominal. En estos casos descritos, el grado de obstrucción del tracto urinario repercutió en el desarrollo de malformaciones letales