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Resección Endoscópica de la Mucosa , Disección , Humanos , Microcirugia , Instrumentos QuirúrgicosAsunto(s)
Aneurisma Infectado/etiología , Aneurisma Infectado/cirugía , Arteria Pulmonar/cirugía , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Aneurisma Falso/diagnóstico , Aneurisma Falso/patología , Aneurisma Falso/cirugía , Aneurisma Infectado/diagnóstico , Aneurisma Infectado/patología , Angiografía , Broncoscopía , Femenino , Humanos , Pulmón/patología , Neumonectomía , Arteria Pulmonar/patología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Pulmonary paraganglioma is a very rare condition with 40 cases reported in the literature. In the vast majority of cases the correct diagnosis could not be yielded preoperatively. CASE PRESENTATION: We report a case of paraganglioma of the lung. Computed tomographic scan showed a solitary pulmonary nodule. Diagnostic thoracotomy was performed and a tumor in the left lower lobe was resected. Frozen section evaluation showed an epithelial tumor with neuroendocrine differentiation and low grade features. Accordingly, lobectomy was performed. The study of the paraffin-embedded specimen yielded furthermore a neuroendocrine differentiated tumor, but mitotic figures were rare. Immunhistochemically the final diagnosis paraganglioma was made. CONCLUSION: In patients with pulmonary paraganglioma, the correct preoperative diagnosis is in general not available. Solitary pulmonary nodules or minor tumors of unknown histology are resected by wedge resection and sent to frozen section evaluation. Frozen section evaluation results in the diagnosis neuroendocrine tumor with more or less mitoses and mostly specified as carcinoid tumor. According to the literature biologic behaviour of carcinoid tumor and pulmonary paraganglioma is similar and thus the incorrect result of frozen section evaluation leads to a correct resection mode. If frozen section evaluation shows low grade features, surgical overtreatment may occur.
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Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Paraganglioma/patología , Paraganglioma/cirugía , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
The vascular endothelial growth factors VEGF-C, VEGF-D and its receptor, VEGFR-3, are overexpressed in different malignancies and associated with lymph node metastasis and poor prognosis. We analysed these factors in clear cell (ccRCC) and papillary (pRCC) renal cell carcinoma (RCC). The results were correlated with various clinicopathological parameters (CPP). We constructed a tissue microarray with tumor samples of 135 (81%) ccRCC and 31 (19%) pRCC. After immunohistochemical staining using polyclonal antibodies for VEGF-C, VEGF-D and VEGFR-3, a semiquantitative analysis was performed to determine the levels of expression. The results were compared between the two subgroups and were correlated with CPP. In the two subgroups the expression of VEGF-C was significantly correlated with that of VEGF-D (p<0.001). There was an increased expression of VEGF-C in 11% of ccRCC and 36% of pRCC (p=0.002). VEGF-D expression was positive by means of analysis in 22% of ccRCC and 42% of pRCC (p=0.039). There was no significant difference regarding the expression of VEGFR-3 between the subgroups (44% ccRCC and 61% pRCC, p=0.11). No correlation was found between the expression of the analysed parameters and CPP (TNM, grading, progression-free survival and overall survival) in either the entire group or in the two subgroups. In summary, ccRCC and pRCC show a different expression pattern of the analysed lymphangiogenic factors. Further studies are necessary to confirm these results and to determine whether the VEGF-C/VEGF-D/VEGFR-3-axis can play a role as a prognostic tool or a target for therapeutic intervention in renal cell carcinoma.
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Carcinoma de Células Renales/química , Neoplasias Renales/química , Linfangiogénesis , Factor C de Crecimiento Endotelial Vascular/análisis , Factor D de Crecimiento Endotelial Vascular/análisis , Receptor 3 de Factores de Crecimiento Endotelial Vascular/análisis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/fisiopatología , Humanos , Inmunohistoquímica , Neoplasias Renales/patología , Neoplasias Renales/fisiopatología , Persona de Mediana EdadRESUMEN
Telomerase is upregulated in some preneoplastic lesions and overexpressed in the majority of malignant tumors, but absent in most nonneoplastic somatic tissues. We analyzed telomerase activity using TRAP-assay in capsule tissues in a rat model with chronic inflammation and in tumor, and visualized the catalytic subunit of telomerase (hTERT) by immunhistochemistry. Significant elevated telomerase activity was found in tumor tissue compared with nonneoplastic tissue (p = 0.047). Cases with a strong inflammation in capsule tissue showed a specific telomerase activity. In these cases, there were no significant differences in telomerase activities compared with malignant tumor tissue. We demonstrate elevated telomerase activity and its diagnostic limits around model implants in a rat model, and visualize its expression not only in malignant tissue but also in inflammatory cells. So the quantitative measurement of telomerase activity should not be applied in general as a marker for malignancy in capsule tissue.
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Dominio Catalítico , Inflamación/enzimología , Sarcoma/enzimología , Telomerasa/metabolismo , Animales , Biomarcadores/análisis , Biomarcadores de Tumor/análisis , Enfermedad Crónica , Inflamación/diagnóstico , Neoplasias Experimentales/diagnóstico , Neoplasias Experimentales/patología , Ratas , Sarcoma/diagnóstico , Sarcoma/patologíaRESUMEN
PURPOSE: VECF-C, -D and their receptor Flt-4 are associated with lymph node metastasis and a poor prognosis in many tumour entities. We have analysed the expression of these factors in transitional cell carcinoma of the bladder with positive lymph nodes. MATERIALS AND METHODS: We constructed "tissue microarrays" (TMAs) from bladder cancer specimens (BC-array) and corresponding lymph node metastases (LN-array) of 73 patients, who all underwent radical cystectomy and bilateral lymphadenectomy. After immunohistochemical staining, semiquantitative analysis was performed using polyclonal antibodies for VEGF-C, -D and Flt-4. The results were correlated with various histopathological and clinical variables. RESULTS: VEGF-C (p = 0.007) and Flt-4 (p = 0.019) were significantly higher expressed in the LN-array compared to the BC-array. In the LN-array VEGF-D correlated with T-(p = 0.013) and N-stage (p = 0.030) Flt-4 correlated with N-stage (p = 0.011) and distant metastasis (p = 0.011) in the BC-array, as well as with T-(p = 0.004) and N-stage (p = 0.014) in the LN-array. Accordingly, in the LN-array VEGF-D positive patients showed both a shorter disease-free survival (p = 0.028) and a poorer overall survival (p = 0.014). Similarly, Flt-4 positive patients had a shorter overall survival (p = 0.033). CONCLUSIONS: Patients with transitional bladder cancer and lymph node metastasis have a poorer prognosis when they overexpress VEGF-D and Flt-4 in their lymph nodes. Pharmacological targeting of these factors could improve their overall survival.
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Biomarcadores de Tumor , Carcinoma de Células Transicionales/diagnóstico , Metástasis Linfática/diagnóstico , Neoplasias de la Vejiga Urinaria/diagnóstico , Factor C de Crecimiento Endotelial Vascular/metabolismo , Factor D de Crecimiento Endotelial Vascular/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/cirugía , Cistectomía , Interpretación Estadística de Datos , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factores de Tiempo , Análisis de Matrices Tisulares , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugíaAsunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Transicionales/genética , Metástasis Linfática/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias de la Vejiga Urinaria/genética , Biopsia , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Pronóstico , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patología , Factor C de Crecimiento Endotelial Vascular/genética , Factor D de Crecimiento Endotelial Vascular/genética , Receptor 3 de Factores de Crecimiento Endotelial Vascular/genéticaRESUMEN
Isolated noncompaction of the left ventricular myocardium is a rare cardiomyopathy typically showing a "spongy" myocardium on ultrasound. We report on the ultrasonic and pathomorphological characteristics of an infant who, at the age of 40 days, was treated by heart transplantation for isolated noncompaction. Noncompaction should be suspected in newborns with otherwise unexplained cardiomyopathy and a "spongy" left ventricle. However, ultrasonic and pathological findings may be much less pronounced at this age than later in life.
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Cardiomiopatía Hipertrófica/congénito , Cardiomiopatía Hipertrófica/cirugía , Trasplante de Corazón , Fibrosis Endomiocárdica/etiología , Atrios Cardíacos/anomalías , Ventrículos Cardíacos/anomalías , Humanos , Lactante , Masculino , Miocitos Cardíacos/patología , Complicaciones Posoperatorias/etiologíaRESUMEN
Various microsatellite and CGH studies in prostate cancer identify deletions on the short arm of chromosome 8 especially at band 8p21-22 searching for unknown putative tumor suppressor genes. By means of microsatellite markers several candidate genes were detected which may play different roles in early prostate cancer progression. We established a quantitative gene dosage PCR based on the real time PCR method serving the purpose of genomic fine mapping. Therefore we used 10 Assays-on Demand (ABI) for the detection of deletions located between and nearby the microsatellite markers D8S258 and NEFL spanning a genomic region of approximate 7 mbp. Comparative immunohistochemical analysis from tissue micro arrays (TMA) of 1122 independent cases followed. We were able to detect three clearly separated deletion intervals on 8p21-22. One on LZTS1, second on NEFL and third a deletion hot spot on LOXL2, which was affected in 72% of all investigated cases. Our comparative immunohistochemical TMA based studies demonstrate that LOXL2 is nearly lost in most prostate cancer tissues. LOXL2 catalyze the crosslinking of collagen and elastin in the extracellular matrix and it has been assumed that it is involved in tumor suppression and cell adhesion. LOXL2 is frequently expressed in proliferating tissues and shows a high expression in benign prostate tissue too. In prostate cancer the expression is positive correlated with the MIB1-score.
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Cromosomas Humanos Par 8 , Dosificación de Gen , Eliminación de Secuencia , Mapeo Cromosómico , Humanos , Masculino , Repeticiones de Microsatélite , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Neoplasias de la Próstata/genéticaRESUMEN
Capsule fibrosis and other complications around various filled breast implants were evaluated in a rat radiation model after 12 months of implantation. Model implants, one per rat, were implanted subcutaneously. One month after subcutaneous implantation, high voltage radiation followed one half each group. A higher rate of capsule fibrosis occurred in radiated animals. Malignant tumors at the implantation site developed in 40% of radiated and 24% of non-radiated animals, with a much higher rate of mitosis in the radiated group (Mann-Whitney, P=0.008). The presence of an implant is a cofactor for tumor development in rats (chi2-test, chi2=6.927; P=0.008) as well as radiation, since none of the control animals developed tumors. Applied to humans, capsule contracture (fibrosis) is a common complication of radiation, while development of radiation-induced sarcoma is a rare complication after postoperative radiotherapy by all account. Still further long-term follow-up human studies are necessary.
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Implantes de Mama/efectos adversos , Contractura/patología , Fibrosarcoma/radioterapia , Fibrosarcoma/cirugía , Reacción a Cuerpo Extraño/etiología , Neoplasias Inducidas por Radiación/patología , Animales , Fibrosis , Inmunohistoquímica , Masculino , Modelos Animales , Diseño de Prótesis , Radioterapia/efectos adversos , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: The Her2/neu oncoprotein, belonging to the erbB-receptor family, is known to contribute to physiological mechanisms of cell proliferation by intrinsic tyrosine-kinase-activity. Overexpression has been shown for several tumors and is known to influence malignant cell proliferation, metastasis and angiogenesis. The clinical use of Her2-targeting agents has emerged in clinical research. In our study, we analyzed Her2/neu expression in urothelial tumors. MATERIALS AND METHODS: Her2/neu expression was evaluated immunohistochemically (IHC) in 127 patients undergoing radical cystectomy (DAKO- Herceptest). Additionally, fluorescent-in-situ-hybridisation (FISH) was carried out in all immunohistochemically "2+" cases (n = 41) to assess gene amplification. After grading the Her2/neu-overall status, Her2/neu expression was correlated with clinicopathological parameters and survival data. RESULTS: An immunohistochemical Her2/neu expression was found in 95 of 127 cases (74.8 %). Of all 41 cases with "2+" staining (32.2 %), 11 cases (26.8 %) showed positive amplification by FISH. Therefore, including the IHC 3+ cases, a Her2/neu overall status of 22 positive (17.3 %) tumors was assessed. Correlation with clinical data showed a relation to lymph node metastasis (P = 0.06), lymph vessel invasion (P = 0.07) and metastasis (P = 0.002). No further associations with other parameters nor with overall survival (P = 0.73) or disease-free survival (P = 0.63) were found. CONCLUSIONS: Her2/neu upregulation is found in invasive bladder cancer with significant differences in protein expression and gene amplification. The association with lymphogenic and distant metastases implicates a late event in carcinogenesis. Moreover, there was no further association with clinicopathological parameters and survival. The possible role of a molecular targeted therapy of advanced bladder cancer with Her2/neu targeting agents should be assessed in further clinical trials.
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Genes erbB-2/genética , Receptor ErbB-2/genética , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/cirugía , Cistectomía , Interpretación Estadística de Datos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Factores de Tiempo , Regulación hacia Arriba , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
PURPOSE: Cyclooxygenase-2 (Cox-2) contributes to the carcinogenesis of human tumors by various mechanisms. As Cox-2-expression has been found in most human neoplasms, selective Cox-2-inhibitors could be used as a molecular targeted therapy, and first clinical trials have already been initiated. Moreover, Cox-2-inhibitors have been shown to add to the activity of conventional cytotoxic therapies in experimental and clinical studies. We analyzed Cox-2-expression in bladder cancer and its implications on clinical parameters. MATERIALS AND METHODS: Cox-2-expression was evaluated immunohistochemically in 157 patients undergoing radical cystectomy. Sixty-two patients had received cisplatin-based treatment during follow-up, either as adjuvant therapy or for metastatic disease. Cox-2-expression was correlated with clinical and pathological parameters, survival data and outcome of chemotherapy. RESULTS: Cox-2 was expressed in 83.4 % of tumors. No association was found with TNM-staging and histological grading, but a significant relation to the histologic subtype (transitional vs. squamous cell carcinoma, p = 0.038) was present. Survival analysis showed no impact of Cox-2-expression on overall or disease-free survival. However, a subgroup of chemotherapy patients demonstrated a significant correlation of strong Cox-2-expression with worse overall survival time (p = 0.01). CONCLUSIONS: Cox-2-expression was found in the majority of invasive bladder tumors. For patients who underwent chemotherapy, a significant relation of Cox-2-expression and worse overall survival was demonstrated. Cox-2 seems to be an interesting molecular target for the diagnosis and therapy of bladder cancer. Further experimental and clinical studies are warranted to elucidate whether Cox-2-inhibition can serve as an additive therapy to chemotherapy of bladder cancer.
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Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Transicionales/enzimología , Inhibidores de la Ciclooxigenasa/uso terapéutico , Isoenzimas/antagonistas & inhibidores , Isoenzimas/análisis , Prostaglandina-Endoperóxido Sintasas/análisis , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/enzimología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/cirugía , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Terapia Combinada , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa/administración & dosificación , Cistectomía , Supervivencia sin Enfermedad , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Isoenzimas/metabolismo , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Prostaglandina-Endoperóxido Sintasas/metabolismo , Análisis de Supervivencia , Factores de Tiempo , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
BACKGROUND: Recent scientific studies have failed to determine parameters for the assessment of prostate cancer aggressiveness. The present study deals with the detection of blood-borne cancer cells based on polymerase chain reaction (PCR) and cell enrichment methods. The contradictory results reported in the literature have called into question the clinical usefulness of this diagnostic method in the preoperative staging of clinically localized prostate cancer. METHODS: We established a combined method of density gradient centrifugation and immunomagnetic separation using epithelium-specific antibodies, i.e. cytokeratins, to isolate prostate-derived circulating cells from the peripheral blood of patients with prostate cancer. Isolated cells were characterized by DNA staining and immunocytochemistry using antibodies for the detection of prostate-specific antigen (PSA), proliferation-associated proteins (MIB-1, H1 and H3) and apoptosis-associated proteins (M30, c-FasR). RESULTS: We applied these methods to 68 prostate cancer patients and were able to isolate cell clusters in 98%. Immunophenotypic and morphological characterization of PSA-positive prostate-derived cell clusters found in the peripheral blood of prostate cancer patients showed two main populations: 1) in 35% of the investigated prostate cancer patients we detected rounded cell aggregates of probable cancer cells expressing proliferation-associated proteins and lacking apoptosis-associated protein expression; 2) in all cases there was a high frequency of circulating dysmorphic cell clusters positive for apoptosis-associated protein expression. CONCLUSION: Our results demonstrate the existence of at least two different types of blood-borne prostate-derived circulating cell clusters. Of these, only the less frequent, round, small cell clusters harbor features that are probably necessary for the cells to survive for metastatic spread.
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Biomarcadores de Tumor/sangre , Células Sanguíneas/citología , Inmunofenotipificación/métodos , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/metabolismo , Línea Celular Tumoral , Proliferación Celular , Centrifugación por Gradiente de Densidad , ADN/metabolismo , Células Epiteliales/metabolismo , Humanos , Inmunohistoquímica , Queratinas/metabolismo , Masculino , Invasividad Neoplásica , Metástasis de la Neoplasia , Reacción en Cadena de la Polimerasa , Antígeno Prostático Específico/sangreRESUMEN
We studied the capsule formation around various filled breast implants and other related changes in distant organs (e.g., liver, spleen, lymph nodes) in a rat model 3 and 6 months after implantation. Model implants, one per rat, (filled with saline, n = 19; silicone, n = 14; cohesive silicone, n = 17; and hydrogel, n = 19) were implanted subcutaneous in the lower back of rats. The animals were sacrificed regularly after 3 and 6 months of implantation or when wound defects occurred. The capsules and organs were examined histologically, and immunohistology of the capsules was performed. A monoclonal antibody specific for AIF-1 (allograft inflammatory factor 1) was used to detect activated macrophages. Wound defects occurred most frequently after implantation of saline and hydrogel implants. Increased capsule thickness was associated with increased grade of inflammation, fibrosis, and the type of implant filling. There was a significant positive correlation between capsule thickness, presence of chronic inflammation, and AIF-1-positive macrophages (p < 0.0001), indicating that inflammation plays an important role in capsule formation. Remarkably, saline and silicone implants (in absence of local complications) cause only a blande slight fibrosis in capsules after 6 months of implantation, whereas capsules around cohesive silicone implants exhibited a more severe fibrosis with an increased capsule thickness. Most importantly, hydrogel seems to be most potent to induce an inflammatory infiltrate with AIF-1 expressing macrophages at the implantation site, independent of implantation time, and capsules also produced a significant increase in thickness after 6 months.
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Modelos Animales , Prótesis e Implantes/efectos adversos , Animales , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
A 44-year-old patient underwent radical prostatectomy and adjuvant radiotherapy for adenoid cystic carcinoma of the prostate. After 7 years and 3 months he recurred locally and was treated with external beam irradiation. The current follow up comprises 9 years and 5 months at which the patient is asymptomatic with stable disease. Lymph node or distant metastases did never occur and the prostate specific antigen level was always within the normal range.
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Carcinoma Adenoide Quístico/patología , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/patología , Adulto , Carcinoma Adenoide Quístico/radioterapia , Carcinoma Adenoide Quístico/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Factores de TiempoRESUMEN
This meeting report summarizes the presentations of three different groups that are active in the field of flow cytometry (FCM) in relation to diagnosing and classification of proliferative disorders. The report starts with the contribution from Regensburg about the developments in DNA FCM, the progression to dual parameter determinations, and combination of immunophenotyping in combination with DNA. In the second part, the use of FCM for the detection of isolated tumor cells in the peripheral blood from patients with prostate or breast cancer is discussed in a contribution from Münster. In the third part, from Heerlen, the use of multi-parameter FCM on formalin-fixed paraffin-embedded tissues from solid tumors is discussed as a new development and application in routine surgical pathology.