Browsing by Subject "Pathology"

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    A comparative pathological study of three strains of Trypanosoma cruzi in an experimental model
    (Murcia : F. Hernández, 1991) De Diego, J.A.; Penin, P.; Del Rey, J.; Mayer, R.; Gamallo, C.
    Trypanosoma cruzi. the etiological agent of Chaps' cliscase. shows a wide variation in its biological hcl ia\ . io~~dre pending on the geographical distribution of different strains. Moreover. sonic. strains can show; variations with the course of tinic. We have studied the tissular tropism of three strains of T. cruzi, Cali. Buli\,ia and Y. from different geographical origins (Colombia. Bolivia ancl I3rasil respectively) on Swiss inice in order to detect any pnrsihle modification in their behaviour attributable only to parasite but not to host variations. The anatoniopathological stud!! of sections from heart. brain. liver. spleen. lymphatic ganglion. skeletal muscle and colon from Swiss mice infected with these strains has cvidencecl the presence of some important tliscrcpancics hctwecn the tissular tropism expected from thcir former clescriptions. and classical typification and then observed lesions. The greatest variations were found in the Y strain which had been described as eniincntly I-eticulotropic but presented lesions in all the organs except tlie spleen and lymphatic ganglion. We consider that the x~ariationsf ound in our study can only be explained in ternis of changes in the properties of the strains consiclercd. and conclude that the classic typificrrtion techniques based on the constant! of the characteristics of the parasite are not fully reliable for the description and clinical management of some evolving strains.
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    Adenosine deaminase, not immune to a mechanistic rethink in central nervous system disorders?
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Hall, Benjamin; George, Jonathan G.; Allen, Scott P.
    Adenosine deaminase (ADA) is a purine metabolism enzyme that catalyses the breakdown of adenosine and deoxyadenosine. The enzyme is important in several cellular processes, including the innate immune response and cellular differentiation, and it is also an important enzyme for the maintenance of brain homeostasis, in part due to its regulation of adenosine. Aberrant regulation of ADA enzyme activity has been linked to several neurodegenerative diseases and diseases that can result in neurological impairment. However, the mechanisms behind altered ADA regulation and how this leads to the development of neurological dysfunction are poorly characterised. This review summarises the current research on ADA and its role and regulation in disease pathology, with a focus on the central nervous system (CNS) and the neurodegenerative disease, amyotrophic lateral sclerosis (ALS)
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    Adrenomedullin expression in pituitary adenomas and nontumoral adenohypophyses
    (Murcia : F. Hernández, 2008) Lombardero, M.; Kovacs, K.; Horvath, E.; Scheithauer, B.W.; Rotondo, F.; Salehi. F; Lloyd, R.V.
    Summary. Adrenomedullin (ADM) is a novel peptide originally identified in extracts of human pheochromocytoma. It is produced by several tissues, including the pituitary gland. The presence of ADM has been immunohistochemically demonstrated in pathologic pituitary glands, but no systematic study of ADM expression in human pituitary adenomas has been reported. Thus, we investigated ADM immunoexpression in 88 various hormone-secreting and clinically nonfunctioning pituitary adenoma types as well as 30 nontumoral adenohypophyses. Furthermore, ADM immunoreactivity was assessed on a 0 to +3 scale in all samples. We found strong immunoreativity for ADM in normal gonadotrophs also expressing FSH and LH whereas in the other adenohypophysial cell types expression of ADM was mild. Results showed that normal adenohypophyses were strongly immunopositive for ADM (2.18±0.11). Our findings demonstrate that ADM expression in the anterior pituitary is diminished in tumors as compared to the normal gland. The physiologic function of ADM is unknown, but it could act as a paracrine or autocrine factor in the adenohypophysis.
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    Adult-onset Alexander disease with a heterozygous D128N GFAP mutation: a pathological study
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Cabrera Galván, Juan José; Martínez Martin, María Soledad; Déniz García, Daniel; Araujo Ruano, Eduardo; Travieso Aja, María del Mar
    The various forms of Alexander disease (AD) have been linked to heterozygous point mutations in the coding region of the Human glial fibrillary acidic protein (GFAP) gene. The aim of this study was to confirm and characterise an adult variant of AD based on the presence of Rosenthal fibres, which were identified at brain autopsy. We performed histological and immunohistochemical studies and mutation screening by cycle sequencing of exons 1, 4, 6, and 8. A heterozygous D128N GFAP mutation, previously described in three other cases of adult-onset AD (AOAD), was genetically confirmed. The mutation was seemingly sporadic. Symptoms of the female, 65-year-old patient started with occasionally asymmetric motor impairment and concluded, 23 months later, with a lack of spontaneous movement in all four limbs, reduced consciousness, an acute respiratory problem, and eventually lethal exitus. The most striking characteristics were a cerebellar syndrome with subsequent clinical signs due to brainstem and spinal cord involvement. The final diagnosis was based on a complete autopsy, detection of Rosenthal fibres, GFAP, vimentin, alpha B-crystallin, ubiquitin, hsp27, neurofilament, and synaptophysin, and the identification of the corresponding GFAP gene mutation. Blood analyses were positive for ANA and rheumatoid factor. In conclusion, this work describes sporadic, rapidly advancing AOAD in a female patient and links it with other published cases with the same mutation. Reflections are provided on the influence of vasculitis and ANA in AD as well as the presence of Rosenthal fibres in the neurohypophysis.
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    An optimized xylene-free protein extraction method adapted to formalin-fixed paraffin embedded tissue sections for western blot analysis
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Mansour, Anthony G.; Abou Khalil, Pamela; Bejjani, Noha; Chatila, Rajaa; Dagher Hamalian, Carole; Faour, Wissam H.
    Deparaffinization of formalin-fixed paraffin embedded (FFPE) tissues with xylene currently remains a major challenge to the biomedical community. We developed an efficient xylene-free protocol to isolate proteins from archived FFPE human tissue sections. A total of 79 different types of FFPE tissue sections of 8 µm thickness were obtained from various archived FFPE specimens. Deparaffinization was conducted by gently washing each section with around 1 ml of hot distilled water (≈80°C). The deparaffinized tissues were homogenized in lysis buffer, and the isolated proteins were quantified and efficiently resolved using western blot analysis for the presence of Protein kinase B (PKB/AKT) and β-actin. Moreover, a significant amount of proteins was successfully isolated with an average of 2.31 µg/µl. The migration pattern of AKT and β-actin obtained from the specimens was similar to the positive control obtained from protein lysates prepared from in vitro cultured MDA231 cancer cell lines. AKT was successfully identified in all specimens, and β-actin protein was resolved with an efficiency higher than 80%. The entire extraction procedure requires only 20 minutes. This newly developed technique is an efficient, safe, cost-effective, and rapid method to isolate proteins from FFPE tissue sections adequate for molecular analysis.
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    Biological behavior of Leishmania (L.) amazonensis isolated from a human diffuse cutaneous leishmaniasis in inbred strains of mice
    (Murcia : F. Hernández, 2003) Cupolilo, S.M.N.; Souza, C.S.F.; Abreu Silva, A.L.; Calabrese, K.S.; Gonçalves da Costa, S.C.
    After a subcutaneous injection of 104 purified amastigotes of an isolate from a diffuse case of cutaneous leishmaniasis caused by the MHOM/BR/76/Ma-5 strain of Leishmania amazonensis, three inbred mouse strains developed a progressive nodular lesion, which evolved to an ulcerated lesion. Based on these data, mice of BALB/c, C57BL/6 or C57BL/10 could be classified as susceptible. The majority of mice developed metastases in the footpads, ear, tail, nose and oral mucosa. Amputation of the members related to the primary lesion was frequent. Experiments using the limiting dilution analysis showed that there was no correlation between lesion and parasite load. It has been demonstrated that these mouse strains could be considered excellent models for mucocutaneous leishmaniasis when infected with L. amazonensis. Metastatic lesions caused destruction of the nasal region with many parasitized macrophages under the epithelial surface of the nasal mucosa. Bone destruction occurred with an extensive inflammatory reaction presenting macrophages heavily parasitized by amastigotes. The parasites also spread to the periodontal ligament and other structures of the oral cavity, which could induce a severe inflammatory process. This study indicates that both nasal and oral lesions in mice infected by L. amazonensis were characterized by an inflammatory reaction with the presence of a high parasite load within macrophages.
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    BRAF mutation: Current and future clinical pathological applications in colorectal carcinoma
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Yan Seen Ng, Jessica; Tai Lu, Cu; King yin Lam, Alfred
    The aims are to review the relevance of the BRAF mutations in the clinical settings of colorectal carcinoma. All the literature concerning BRAF mutations and colorectal carcinoma published in PubMed from 2010 to 2018 was reviewed. Multiple variants of BRAF mutations exist in colorectal cancer, the most common type being V600E. The mutation is found in 5 to 15% of colorectal carcinomas and is less common in Asian populations. BRAF mutations are linked with older age, female gender, cigarette smoking and are more common in the right (proximal) portion of the large intestine. BRAF mutations are associated with carcinomas of high histological grade and advanced cancer stages. Often BRAF mutated carcinomas demonstrate adverse histological features such as lymphovascular invasion, perineural invasion, tumour budding and lymph node metastases. BRAF mutations are found in serrated polyposis syndrome and have a negative correlation with hereditary nonpolyposis colorectal cancer (HNPCC). An array of methods of detection of BRAF mutation in colorectal carcinoma are available, such as immunohistochemistry and next generation sequencing, etc. Combinatorial approaches involving anti-BRAF therapies targeting both MAPK signalling as well as the PI3K/mTOR pathway could be a new approach for treatment of metastatic colorectal carcinoma. To conclude, BRAF mutation is important in the pathogenesis of colorectal cancer. Further research on the detection method as well as its role in target therapy will help to improve the management of patients with colorectal cancer
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    Characteristic abnormal expression of galectin-3 in serrated colon lesions and its pathological significance
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zhou, Zhiyi; Huang, Dandan; Cai, Ying; Yang, Shudong; Jiang, Nanxing; Zhang, Qiang
    Serrated lesions are precursors of some colon cancers. The expression of galectin-3 has been reported to be involved in BRAF and KRAS mutations (the key pathogenic drivers of serrated lesions). This study aimed to investigate the expression intensity and subcellular localization of galectin-3 in serrated colon lesions by immunohistochemistry. The results demonstrated that, regarding expression intensity, galectin-3 expression in serrated colon lesions was significantly upregulated; regarding subcellular localization, the membrane expression of hyperplastic polyps/ sessile serrated lesions (HP/SSL) was weakened, the structure was disorganized and that of traditional serrated adenoma (TSA) was significantly weakened or disappeared, and the nuclear expression of both was positive; in the dysplasia of SSL (SSL-D) and TSA (TSA-HD), galectin-3 expression intensity remained high, and was weakened or disappeared in some nuclei, the expression disorder of the SSL-D cell membrane was reduced, the polarity of the cell was restored, weak expression appeared in the local cell membrane of TSA-HD, and the "serrated" structure of both was reduced or disappeared and seemed to revert more to that seen in common adenomas. In summary, abnormal galectin-3 expression occurs in the early stages of serrated lesions, its expression is characteristic, the dynamic changes in galectin-3 expression are closely related to the histopathological changes and progression of serrated lesions, and further accumulated molecular alterations contribute to this process.
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    Elogio de la melancolía: una historia marginal de la bilis negra
    (Universidad de Murcia. Servicio de Publicaciones, 2016) Horacio De Freitas, Juan
    Este ensayo se desarrolla a partir de la siguiente hipótesis: hay, por lo menos, dos historias posibles de la melancolía. No se trata, sin embargo, de historias indiferentes entre sí, sino más bien de historias entrecruzadas que pretenden ignorarse una a la otra, que se confunden, dialogan y se enfrentan a lo largo de su transcurso. Nos permitiremos elaborar una pequeña genealogía que nos permita comprender la forma en la que nacieron estas dos presuntas historias de la melancolía a las que hacemos referencia, y así mostrar las diferentes transformaciones por las cuales ha pasado la bilis negra, sustancia que ha sido asociada con fenómenos tan disímiles entre sí como lo patológico, la genialidad e, incluso, lo humorístico.
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    Estudio anatomopatológico y mastocitos en hígados de ternero decomisados en matadero
    (Universidad de Murcia. Servicio de publicaciones, 2022) Bas Murcia, Ana de los Ángeles; Sánchez Martínez, Pedro; Gómez Sánchez, Miguel Ángel; Bernabé Salazar, Antonio
    Este estudio aborda las alteraciones anatomopatológicas y el número de mastocitos en 51 hígados de ter-nero decomisados en un matadero importante del sur-este de España. El análisis microscópico se ha realizado con las tinciones hematoxilina-eosina (H-E) y Tricrómico de Masson (TRC). Además, se determinó el núme-ro de mastocitos en función de sus patologías, mediante la tinción azul de toluidina, haciendo un conteo en 10 campos de 348 x 263 μm a 40x en cada una de las muestras. Con el programa estadístico SPSS y las pruebas estadísticas Kolmogorov-Smirnov y Mann-Whitney se ha hecho una comparación con 5 hígados control. Las lesiones anatomopatológicas causantes de decomiso han sido: abscesos (47%), colangiohepatitis (31%), fibrosis (8%), esteatosis (6%), atrofia (2%), necrosis (2%), congestión (2%) y quiste (2%). Clasificándose en lesiones inflamatorias (49%), lesiones parasitarias (33%) y lesiones degenerativo-metabólicas (18%). Los re-sultados del conteo de mastocitos muestran que hay diferencias significativas en el número de mastocitos de los hígados con colangiohepatitis (p 0,001), respecto a los hígados control y no hay diferencias significativas en los hígados con abscesos (p 0,227). Al hacer una clasificación por familias de las alteraciones anatomopa-tológicas estudiadas se ha llegado a la conclusión de que no hay diferencias significativas en las alteraciones inflamatorias al compararlas con el grupo control y sí las hay en las alteraciones parasitarias. Las alteraciones degenerativas también muestran diferencias significativas, pero el número de muestras recogidas es bajo.
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    Estudio clínico y morfológico del borde dorsal del cuello en caballos cruzados lusitanos sometidos a ejercicio de alta intensidad en Barranco (Portugal)
    (Murcia: Servicio de Publicaciones de la Universidad de Murcia, 2013) Morales, Abelardo; Méndez, A.; Méndez Angulo, J.; Saldivar, S.; Lamprea, A.; Díaz García, M.
    Se plantea como objetivo un estudio clínico y morfológico del borde dorsal del cuello en caballos cruzados Lusitanos sometidos a ejercicio de alta intensidad en Barranco (Portugal). Fueron estudiados un total de 21 caballos (14 machos castrados y 7 yeguas), con edades comprendidas entre 5-12 años, cruzados de la raza Lusitana en Barranco, Portugal. Los equinos habían sido sometidos a ejercicio de alta intensidad, tiempo y a las mismas condiciones de alimentación y manejo. Se practicó un examen clínico asi como un estudio morfológico considerando condición corporal y peso; por último se midió el perímetro cervical. No se observaron lesiones cervicales a la inspección y palpación, ni deformación del borde dorsal del cuello en ninguno de los casos estudiados. El estudio morfológico evidenció Puntuación 0 y 1.- ningún caballo bajo estas categorías. Puntuación 2.- 12/21 (57%) Puntuación 3.- 9/21 (43%). Puntuación 4 y 5.-ningún caballo bajo estas categorías. Perímetro cervical, el promedio del diámetro del cuello fue de 91.82 cm, el promedio de la longitud del cuello fue de 85.76 cm y el peso fue de 388.19 Kg. Los resultados estadísticos del peso versus el perímetro cervical del cuello presentaron un coeficiente de correlación de 0.403 y para el grado puntuación del cuello obeso y condición corporal fue de 0.272. En conclusión, no se observaron lesiones compatibles con la deformación del borde dorsal del cuello en caballos cruzados Lusitanos.
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    Evaluación cuantitativa y cualitativa de la satisfacción en la enseñanza de la Patología en estudiantes de medicina en una universidad compleja chilena
    (Universidad de Murcia. Servicio de publicaciones, 2024) Durán Reyes, Cristina; Delgado Schneider, Carolina; Martínez Riquelme, Santiago; Maturana Barrera, Jorge; Constanzo Valdebenito, Claudia; Burgos Burgos, Diego; Dassori Walker, Valeria; Vallejos, Anai; Villalobos Huerta, Pía
    Las asignaturas de Patología general y Anatomía patológica son impartidas durante elquinto y sexto semestre de la carrera de Medicina de la Universidad de Concepción. En estas seutiliza un estilo de enseñanza tipo aula invertida con una actividad práctica de “Diseño de casosClínico-Patológicos” (DCCP), iniciada en sala de patología quirúrgica, donde los estudiantesvivencian en forma real el trabajo del anatomopatólogo en grupos de 3 a 4 personas, realizandodesde el dictado macroscópico hasta el diagnóstico microscópico, con una presentación final delcaso a estudiantes y docentes. Se realizó un estudio observacional analítico transversal a unamuestra de 87 estudiantes que cursaron ambas asignaturas. Se efectuó un análisis descriptivocuantitativo y un método cualitativo de análisis de contenido, codificándose y clasificándose lasrespuestas de2 instrumentos. La satisfacción general de la actividad DCCP fue del 82,4%, siendopercibida como innovadora y útil para el desarrollo de habilidades y aprendizajes teóricos depatología, que prepara a los alumnos de mejor manera para enfrentar los desafíos del mundo realcomo profesionales de la salud. No se debe olvidar la importancia de considerar las preferencias ynecesidades de los estudiantes al diseñar estrategias de enseñanza. La evaluación cualitativa de laactividad DCCP y de las asignaturas entregó valiosa información para un mejoramiento continuo;reafirmando la importancia de incorporar éstas en las evaluaciones de prácticas docentes. Se concluye que la actividad práctica DCCP ayuda de mejor forma a los estudiantes de medicina a entender los aspectos macroscópicos y microscópicos de la Anatomía Patológica; superando incluso al aula invertida. La combinación de enfoques centrados en el alumno, trabajo en entornos reales,un apoyo docente adecuado y material de estudio de calidad puede conducir a una experiencia de aprendizaje más efectiva y satisfactoria para los estudiantes en estas disciplinas.
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    G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels: Molecular, cellular, and subcellular diversity
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Martín Belmonte, Alejandro; Aguado, Carolina; Alfaro Ruíz, Rocio; Luján, Rafael
    G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels are mainly expressed in excitable cells such as neurons and atrial myocytes, where they can respond to a wide variety of neurotransmitters. Four GIRK subunits have been found in mammals (GIRK1-4) and act as downstream targets for various Gαi/o-linked G protein-coupled receptors (GPCRs). Activation of GIRK channels produces a postsynaptic efflux of potassium from the cell, responsible for hyper-polarization/inhibition of the neuron. A growing body of evidence suggests that dysregulation of GIRK signalling can lead to excessive or deficient neuronal excitability, which contributes to neurological diseases and disorders. Therefore, GIRK channels are proposed as new pharmacological targets. The function of GIRK channels in neurons is not only determined by their biophysical properties but also by their cellular and subcellular localization patterns and densities on the neuronal surface. GIRK channels can be located within several subcellular compartments, where they have many different functional implications. This subcellular localization changes dynamically along the neuronal surface in response to drug intake and following plasticity processes. Ongoing research is focusing on determining the proteins that form macromolecular complexes with GIRK channels and are responsible for fast and precise signalling under physiological conditions, and how their alteration is implicated in pathological conditions. In this review, the distinct regional, cellular, and subcellular distribution of GIRK channel subunits in the brain will be discussed in view of their possible functional and pathological implications.
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    Genetic alterations and histopathologic findings in familial renal cell carcinoma
    (Murcia : F. Hernández, 2006) Hansel, D.E
    Renal cell carcinoma is increasing in frequency in the United States and is often detected late in the course of disease due to nonspecific symptoms. A subset of renal cell carcinoma is attributable to familial or hereditary syndromes, including von Hippel-Lindau and Birt-Hogg-Dubé syndromes, among others. Understanding of the molecular alterations in patients with familial syndromes may provide some insight into the underlying mechanisms of disease initiation and progression. This review describes the various subtypes of renal cell carcinoma and the familial syndromes associated with these tumors.
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    Glomerular pathology in surviving pigs experimentally infected with african swine fever virus
    (Murcia : F. Hernández, 1991) Martín Fernández, José Javier; Igual, A.; Rueda, A.; Sánchez-Vizcaino, J.M.; Alonso-Martí, C.
    Twelve miniature pigs were inoculated with an attenuated African swine fever virus to study glomerular involvement in surviving pigs. In acute phase. kidneys were severely affected and displayed a glomerular capillary thrombosis with fibrin deposition in vascular lumen, detected by immunofluorescence. Fibrin-positive deposits were progressively cleared between one to three months after infection in surviving pigs. The histological picture in kidneys of surviving pigs, up to one post-infection year, showed a focal and segmental glomerulonephritis with hyalinosis, and IgM and C3 deposition was detected by immunofluorescence. Its pathogeny as an evolutive stage of acute glomerular injury is pointed out.
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    Hepatocellular carcinoma in non-alcoholic fatty liver disease (NAFLD) - pathological evidence for a predominance of steatohepatitic inflammatory non-proliferative subtype
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Campos de, Priscila B.; Oliveira, Claudia P.; Stefano, José T.; Martins-Filho, Sebastião N.; Chagas, Aline L.; Herman, Paulo; Albuquerque de, Luiz C.; Alvares-da-Silva, Mário R.; Longatto-Filho, Adhemar; Carrilho, Flair J.; Alves, Venancio A.F.
    Objectives. This study evaluated clinical and pathological aspects of patients with hepatocellular carcinoma (HCC) secondary to non-alcoholic fatty liver disease (NAFLD) and related these factors to immunohistochemical markers representative of the proliferative class. Methods. We evaluated 35 HCC nodules from 21 patients diagnosed with NAFLD undergoing liver resection (n=12) or liver transplantation (n=8) or both (n=1). Demographic, clinical and biochemical data were compared to histological features and to immunohisto- chemical reactivity for K19 and Ki-67. Results. Cirrhosis was present in 58% of patients. Ages ranged from 50 to 77 years. Sixteen patients (76%) were male and had type 2 diabetes mellitus, 81% had arterial hypertension, and 90% had BMI above 25 kg/m 2. Alpha-fetoprotein levels were normal in 62% of patients. Twenty-five (70%) nodules were diagnosed as “steatohepatitic HCC”. Only 32% of the nodules presented high levels of Ki-67 (>10%) and/or K19 (>5%), although 63% were poorly differentiated (G.3/G.4) according to Edmondson & Steiner grading system. K19 positivity (>5%) was associated with higher degree of intratumoral inflammation (G.2/G.3), and with fibrosis, both at the center of the tumor and at the tumor front, whereas Ki-67 positivity (>10%) was associated with ballooning of neoplastic cells and occurred in more than 70% in non-cirrhotic patients. Conclusion. NAFLD-related HCC was found in non- cirrhotic patients in 42% of cases, alpha-fetoprotein level was normal in 63% and "steatohepatitic HCC" was the predominant histological type. Immunoexpression of K19 and/or Ki-67 occurred in 32% of the nodules and were associated with intratumoral inflammation and ballooning, suggesting that HCC in MtS may be preferentially “an inflammatory, non-proliferative subtype of HCC”
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    High expression of DEK is associated with poor prognosis in hepatocellular carcinoma.
    (Celular e Histiologia Universidad de Murcia, Departamento de Biologia, 2019) Lee, Soo Yeon; Jung, Wonkyung; Lee, Jinhwan; Kim, Aeree; Kim, Han Kyeom; Kim, Baek-Hui
    DEK is an oncogene that has been identified as part of the DEK-CAN fusion gene. DEK plays a role in carcinogenesis through WNT signaling and induces cell proliferation through cyclin-dependent kinase signaling. DEK overexpression has been reported in HCC, but the clinical significance is unclear. This study enrolled 221 cases of HCC. The expression of DEK protein was evaluated by immunohistochemical staining. Cdk4, cyclin D1, Wnt10b, E-cadherin, and β-catenin were also immunohistochemically stained and analyzed for correlation. The association of clinicopathologic factors with DEK expression was analyzed. DEK expression was observed in 44.8% (99/221) of cases. DEK expression showed a statistical association with clinicopathologic factors, including Edmondson-Steiner grade, presence of vascular emboli, and multiplicity (p<0.05). Among the other IHC markers, the expression of cdk4 was correlated with DEK expression (p<0.05). Patients with high DEK expression showed a significantly lower overall survival rate (p=0.006). However, the disease-free survival rate did not differ significantly. In addition, in a Cox regression model analysis, DEK expression was an independent prognostic factor. In summary, high expression of DEK was observed in HCC and was associated with poor prognostic marker expression and poor prognosis.
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    High-resolution three-dimensional visualization of hepatic sinusoids in cirrhotic rats via serial histological sections
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Liu, Jing-Yi; Lv, Wen-Juan; Jian, Jian-Bo; Xin, Xiao-Hong; Zhao, Xin-Yan; Hu, Chun-Hong
    Aim. As a specialized intraparenchymal vascular conduit, hepatic sinusoids play a key role in liver microcirculation. This study aimed to explore the three-dimensional (3D) morphological changes of cirrhotic sinusoids by serial histological sections. Methods. Cirrhosis was induced by tail vein injection of albumin in Wistar rats with a positive antibody. A total of 356 serial histological sections were prepared from liver tissue blocks of normal and cirrhotic rats. The optical microscope images were registered and reconstructed, and 3D reconstructions of the fine structures of fibrous tissues and sinusoids were subsequently visualized. Results. The fibrosis area of the cirrhotic sample was 6-16 times that of the normal sample (P<0.001). Cirrhosis led to obvious changes in the distribution and morphology of sinusoids, which were mainly manifested as dilation, increased quantity and disordered distribution. Compared with normal liver, cirrhotic liver has a significantly increased volume ratio, number and volume of sinusoids (1.63-, 0.53-, and 1.75-fold, respectively, P<0.001). Furthermore, the samples were further divided into three zones according to the oxygen supply, and there were significant differences in the morphology of the sinusoids in the normal and cirrhotic samples (P<0.05). In particular, morphological parameters of the cirrhotic sinusoids near the portal area were obviously greater than those in the normal liver (P<0.05). Conclusion. 3D morphological structures of hepatic sinusoids were reconstructed, and the adaptive microstructure changes of cirrhotic sinusoids were accurately measured, which has an important implications for the study of hepatic microcirculation and pathological changes of cirrhosis.
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    Histopathological characteristics of liver biopsy performed at different time points in drug-induced liver injury
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Wang, Yu; Ma, Zikun; Guo, Tiantian; Liu, Jimin; Li, Min; Zhao, Xinyan
    Background and Aims. Liver biopsy can provide critical information in patients with druginduced liver injury (DILI). Our study aimed to compare the histopathological features of DILI at different time points from the onset to liver biopsy. Methods: We conducted a single-centre retrospective observational study. The clinical and follow-up data were extracted, and the pathological slides were reviewed. Results. 129 patients were included. The median age was 52 and 75% were women. They were divided into <1 month, 1-3 months, and >3 months groups according to the durations from onset of the disorder to liver biopsy. The aminotransferase, alkaline phosphatase, and bilirubin levels showed no significant differences at onset but significantly decreased with time among the three groups (all p<0.05) at the time of liver biopsy. Histological injury patterns were significantly different among the three groups (p<0.01). Hepatocellular, canalicular, and cholestasis of Kupffer cells were significantly less frequent in the >3 months group (p<0.01). For patients taking herbs, bridging necrosis and cholestatic injury were significantly more frequent in the <1 month group (p<0.01). Furthermore, ductopenia, cholate stasis, and foam-like cells were equally distributed in the three groups but were significantly associated with poor prognosis. Conclusions. Biopsy time significantly affects liver pathology: the earlier, the more acute cholestatichepatitic pattern, the later, the more chronic injury patterns. The prognostic features (ductopenia, cholate stasis, and foam-like cells) occurred equally in all three groups. Our study provides valuable information for liver pathologists aiding in their better interpretation of the liver biopsy from patients with DILI.
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    Histopathological prognostic factors for colorectal liver metastases: A systematic review and meta-analysis of observational studies
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Cavalcante de Oliveira, Cássio Virgílio; Marques Fonseca, Gilton; Pirola Kruger, Jaime Arthur; Sobroza de Mello, Evandro; Ferreira Coelho, Fabricio; Herman, Paulo
    Introduction. Resection is the mainstay of treatment for colorectal liver metastases (CRLMs). Many different histopathological factors related to the primary colorectal tumour have been well studied; however, histopathological prognostic factors related to CRLMs are still under evaluation. Objective. To identify histopathological factors related to overall survival (OS) and disease-free survival (DFS) in patients with resected CRLMs. Methods. A systematic review was performed with the following databases up to August 2020: PubMed, EMBASE, Web of Science, SciELO, and LILACS. The GRADE approach was used to rate the overall certainty of evidence by outcome. Results. Thirty-three studies including 4,641 patients were eligible. We found very low certainty evidence that the following histopathological prognostic factors are associated with a statistically significant decrease in OS: presence of portal vein invasion (HR, 410.50 [95% CI, 0.37 to 0.68]; I2=0%), presence of perineural invasion (HR, 0.55 [95% CI, 420.36 to 0.83]; I2=0%), absence of pseudocapsule (HR, 0.41 [CI 95%, 0.29 to 0.57], p<0.00001; I2=0%), presence of satellite nodules (OR, 0.45 [95% CI, 0.26 to 0.80]; I2=0%), and the absence of peritumoural inflammatory infiltrate (OR, 0.20 [95% CI, 0.08 to 0.54]; I2=0%). Outcome data on DFS were scarce, except for tumour borders, which did not present a significant impact, precluding the meta-analysis. Conclusion. Of the histopathological prognostic factors studied, low- to moderate-certainty evidence shows that vascular invasion, perineural invasion, absence of pseudocapsule, presence of satellite nodules, and absence of peritumoral inflammatory infiltrate are associated with shorter overall survival in CRLMs.