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1.
J Thorac Oncol ; 16(10): 1632-1646, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34139363

RESUMO

Diagnosing a pulmonary neuroendocrine neoplasm (NEN) may be difficult, challenging clinical decision making. In this review, the following key clinical and pathologic issues and informative molecular markers are being discussed: (1) What is the preferred outcome parameter for curatively resected low-grade NENs (carcinoid), for example, overall survival or recurrence-free interval? (2) Does the WHO classification combined with a Ki-67 proliferation index and molecular markers, such as OTP and CD44, offer improved prognostication in low-grade NENs? (3) What is the value of a typical versus atypical carcinoid diagnosis on a biopsy specimen in local and metastatic disease? Diagnosis is difficult in biopsy specimens and recent observations of an increased mitotic rate in metastatic carcinoid from typical to atypical and high-grade NEN can further complicate diagnosis. (4) What is the (ir)relevance of morphologically separating large cell neuroendocrine carcinoma (LCNEC) SCLC and the value of molecular markers (RB1 gene and pRb protein or transcription factors NEUROD1, ASCL1, POU2F3, or YAP1 [NAPY]) to predict systemic treatment outcome? (5) Are additional diagnostic criteria required to accurately separate LCNEC from NSCLC in biopsy specimens? Neuroendocrine morphology can be absent owing to limited sample size leading to missed LCNEC diagnoses. Evaluation of genomic studies on LCNEC and marker studies have identified that a combination of napsin A and neuroendocrine markers could be helpful. Hence, to improve clinical practice, we should consider to adjust our NEN classification incorporating prognostic and predictive markers applicable on biopsy specimens to inform a treatment outcome-driven classification.


Assuntos
Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Neoplasias Pulmonares , Tumores Neuroendócrinos , Humanos , Recidiva Local de Neoplasia
2.
Histopathology ; 56(3): 356-63, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20459535

RESUMO

AIMS: To test the hypothesis that the published morphological criteria permit reliable segregation of small cell carcinoma of the lung (SCLC) and large cell neuroendocrine carcinoma (LCNEC) cases by determining the interobserver variation. METHODS AND RESULTS: One hundred and seventy cases of SCLC, LCNEC and cases diagnosed as neuroendocrine lung carcinoma before LCNEC had been established as a diagnostic category were retrieved from the archives of the assessor's institutes. A representative haematoxylin and eosin section from each case was selected for review. Batches of cases were circulated among nine pathologists with a special interest in pulmonary pathology. Participants were asked to classify the cases histologically according to the 2004 World Health Organization (WHO) criteria. The diagnoses were collected and kappa values calculated. Unanimity of diagnosis was achieved for only 20 cases; a majority diagnosis was reached for 115 cases. In 35 cases no consensus diagnosis could be reached. There was striking variability amongst assessors in diagnosing SCLC and LCNEC. The overall level of agreement for all cases included in this study was fair (kappa=0.40). CONCLUSIONS: Using non-preselected cases, the morphological WHO criteria for diagnosing SCLC and LCNEC leave room for subjective pathological interpretation, which results in imprecise categorization of SCLC and LCNEC cases.


Assuntos
Carcinoma de Células Grandes/epidemiologia , Carcinoma Neuroendócrino/epidemiologia , Neoplasias Pulmonares/epidemiologia , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Células Grandes/classificação , Carcinoma de Células Grandes/diagnóstico , Carcinoma Neuroendócrino/classificação , Carcinoma Neuroendócrino/diagnóstico , Humanos , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico , Variações Dependentes do Observador , Carcinoma de Pequenas Células do Pulmão/classificação , Carcinoma de Pequenas Células do Pulmão/diagnóstico
3.
Cornea ; 26(9): 1118-22, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17893547

RESUMO

PURPOSE: To evaluate the feasibility of the femtosecond (FS) laser in preparation of posterior lamellar discs (PLDs) and to study the effect on endothelial cell (EC) viability for Descemet-stripping endothelial keratoplasty. METHODS: Fourteen human donor bulbi unsuitable for transplantation were used. A horizontal lamellar cut was prepared in the donor cornea with an FS laser by using a raster and/or a spiral spot pattern. The control group consisted of the paired cornea of the same donor. EC density was evaluated before and after preservation in organ culture. The PLD was stripped from the anterior part by using either a forceps or a blunt dissection technique. The damage to the endothelium was evaluated. RESULTS: EC loss after organ storage was not statistically significant between the FS cornea group and the control group in the 15- (7.7% +/- 6.9% and 8.9% +/- 8.1%, respectively; P = 0.78) and 30-kHz (4.3% +/- 4.0% and 3.7% +/- 3.6%, respectively; P = 0.75) group. There was no significant effect of laser frequency (15 vs. 30 kHz) on EC loss (7.7% vs. 4.3%, P = 0.25). Dissection by using a forceps stripping technique resulted in higher EC loss than that with a blunt dissection technique (13.0% vs. 6.5%, P = 0.03). CONCLUSIONS: EC loss after FS laser lamellar cutting is not dependent on the frequency (ie, energy level) of the laser. A blunt dissection technique of PLDs resulted in acceptable EC loss and supports the clinical use of the FS laser for the preparation of PLDs.


Assuntos
Transplante de Córnea/métodos , Lâmina Limitante Posterior/cirurgia , Endotélio Corneano/patologia , Terapia a Laser , Idoso , Contagem de Células , Sobrevivência Celular , Endotélio Corneano/transplante , Estudos de Viabilidade , Feminino , Humanos , Masculino , Técnicas de Cultura de Órgãos
4.
Am J Ophthalmol ; 140(6): 1123-5, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16376661

RESUMO

PURPOSE: To investigate whether the peeled internal limiting membrane (ILM) contains cellular retinal cell fragments, and to learn more about their possible origin. DESIGN: Experimental study. METHODS: ILM peeled from ten eyes during vitrectomy by infracyanine green (ICG) was studied immunohistochemically using the markers: GFAP, S-100, and vimentin. Five ILM specimens were from eyes with diabetic macular edema (DME), two from eyes with a macular hole, and three from eyes with persisting macular edema after retinal detachment surgery. RESULTS: In eight of the ten ILM specimens, we found GFAP-positive staining, indicating the presence of remnants of footplates from Müller cells or glial cells. Two ILM specimens were positive for S-100, indicating the presence of neural cells or ganglion cells. CONCLUSIONS: ILM peeled from the retina during vitrectomy using ICG may contain remnants of Müller cell footplates, neural cells, and ganglion cells.


Assuntos
Corantes , Membrana Epirretiniana/patologia , Verde de Indocianina/análogos & derivados , Vitrectomia , Idoso , Membrana Basal/metabolismo , Membrana Basal/patologia , Membrana Basal/cirurgia , Retinopatia Diabética/cirurgia , Membrana Epirretiniana/metabolismo , Membrana Epirretiniana/cirurgia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Técnicas Imunoenzimáticas , Edema Macular/cirurgia , Masculino , Pessoa de Meia-Idade , Neuroglia/patologia , Descolamento Retiniano/cirurgia , Perfurações Retinianas/cirurgia , Proteínas S100/metabolismo , Vimentina/metabolismo
5.
Cardiovasc Res ; 59(1): 222-33, 2003 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-12829193

RESUMO

OBJECTIVE: Although the application of cold energy, cryotherapy, has been shown to cause selective damage to cellular components with preservation of matrix structure resulting in less fibrosis in a variety of tissues, the effects of intravascular cryotherapy on vessel wall repair after balloon angioplasty are unknown. We sought to characterize the effects of cryotherapy application on vessel wall repair after balloon angioplasty and study the relationship between collagen accumulation in the vessel wall and late lumen loss as assessed by serial intravascular ultrasound. METHODS: The immediate, early (72 h) and late (10 weeks) effects of three intravascular cryotherapy application time periods (60, 120 and 240 s) after iliac artery balloon angioplasty ('cryotherapy') were compared with balloon angioplasty alone ('control') in 59 rabbits. Arterial lumen area was measured by intravascular ultrasound immediately after the procedure, at 72 h and at 10 weeks. Collagen content was calculated separately for intima and media/adventitia layers and correlated with late lumen loss. RESULTS: Cryotherapy produced average vessel wall temperature of -26 degrees C (range, -20 to -45 degrees C) and resulted in significantly larger lumen cross-sectional area (CSA) immediately after application (5.74+/-1.18 vs. 4.14+/-0.75 mm(2), P=0.008) but was not different than control arteries at 10 weeks. At 72 h, there was extensive cell loss in the medial and adventitial layers accompanied by increased macrophage infiltration in cryotherapy treated arteries compared to control. At 10 weeks, intimal hyperplasia was increased 2-fold in cryotherapy treated arteries. Collagen content was increased 2-fold in the medial/adventitial layers, and nearly 3-fold in the intima of cryotherapy treated arteries. Collagen content in arterial intima (P=0.01) as well as media/adventitia (P=0.005) positively correlated with late lumen loss. Foci of chondro- and osseous metaplasia and calcification were evident at the medial-adventitial junction in cryotherapy treated arteries at 10 weeks. CONCLUSION: Intravascular cryotherapy induced early arterial wall cell loss and late intimal hyperplasia, vascular fibrosis and chondro- and osseous metaplastic changes with no late beneficial effects on lumen area compared to balloon angioplasty alone. Collagen accumulation in all three layers of the vessel wall contributes to the development of late inward remodeling after balloon angioplasty.


Assuntos
Crioterapia/métodos , Artéria Ilíaca/lesões , Artéria Ilíaca/patologia , Animais , Caspase 3 , Caspases/análise , Cateterismo/efeitos adversos , Divisão Celular , Colágeno/análise , Elastina/análise , Artéria Ilíaca/diagnóstico por imagem , Masculino , Modelos Animais , Coelhos , Ultrassonografia de Intervenção
6.
Am J Respir Crit Care Med ; 175(5): 464-72, 2007 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-17138956

RESUMO

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with increased numbers of CD8(+) cytotoxic T lymphocytes (CTLs) in the lung, but the functional activity of CTLs remains unknown. Granzyme A (GrA) and B (GrB) are serine proteases considered to be important effector molecules of CTLs and natural killer cells. OBJECTIVE: To investigate protein and mRNA expression of GrA and GrB in peripheral lung tissue from patients with COPD and control subjects with normal lung function. METHODS: Paraffin-embedded sections of surgical lung specimens from 22 patients with COPD (FEV(1), 22% predicted; GOLD stage 4) and 15 control subjects (FEV(1), 108% predicted) were immunostained for GrA and GrB, and semiquantified on a 3-point scale. Messenger RNA expression in total lung, specific cell types enriched for by laser capture microdissection, and freshly isolated primary cells were determined by reverse transcriptase-polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: GrA and GrB immunoreactivity was observed in CD8(+) CTLs and CD57(+) natural killer cells, but also in type II pneumocytes and alveolar macrophages in both groups. Bronchiolar epithelium stained positive for GrA, but negative for GrB. These observations were confirmed by reverse transcriptase-polymerase chain reaction on total lung, laser capture microdissection-enriched specific cell types and freshly isolated primary type II pneumocytes. The scores of GrA-expressing type II pneumocytes were significantly higher in patients with COPD versus control subjects. CONCLUSIONS: GrA and GrB mRNA and protein are detectable in human lung tissue. GrA expression is increased in type II pneumocytes of patients with very severe COPD. These results indicate that GrA may be important in the development of COPD.


Assuntos
Brônquios/enzimologia , Expressão Gênica , Granzimas/genética , Alvéolos Pulmonares/enzimologia , Doença Pulmonar Obstrutiva Crônica , RNA Mensageiro/genética , Brônquios/patologia , Feminino , Seguimentos , Granzimas/biossíntese , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Alvéolos Pulmonares/patologia , Doença Pulmonar Obstrutiva Crônica/enzimologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Índice de Gravidade de Doença
7.
Int J Cardiovasc Imaging ; 22(3-4): 389-92, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16502021

RESUMO

Although acute pericarditis is a common and usual benign disorder, sometimes evolution to constrictive pericarditis may occur. We present a case of constrictive pericarditis late after coronary bypass grafting, complicated by right sided heart failure. Edema formation was aggravated due to protein-losing enteropathy, resulting in hypoalbuminemia. Imaging of constrictive pericarditis was done by ultrasound as well as simultaneous pressure recording of the right and left ventricle. Imaging of intestinal protein loss was possible using intravenous Technetium-99m-labelled human serum albumin.


Assuntos
Pericardite Constritiva/diagnóstico por imagem , Enteropatias Perdedoras de Proteínas/diagnóstico por imagem , Idoso , Ecocardiografia Doppler , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Compostos de Organotecnécio , Pericardiectomia , Pericardite Constritiva/patologia , Pericardite Constritiva/cirurgia , Pericárdio/diagnóstico por imagem , Pericárdio/patologia , Pericárdio/cirurgia , Enteropatias Perdedoras de Proteínas/patologia , Enteropatias Perdedoras de Proteínas/cirurgia , Cintilografia , Albumina Sérica
8.
Biol Neonate ; 88(3): 156-63, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15942164

RESUMO

BACKGROUND: Experimental observations in mammalian models suggest that endothelial nitric oxide (NO) synthase (NOS) content and activity are decreased in persistent pulmonary hypertension of the newborn. OBJECTIVES: To test the hypothesis that disruption of NO signaling in the developing chick embryo lung may contribute to pulmonary hypertension. METHODS: We analyzed pulmonary arterial reactivity and structure and heart morphology of 19-day chick embryos (incubation time 21 days) that received a daily injection of the NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 20 mug per gram egg) or vehicle from day 12 until day 18. RESULTS: Exposure to L-NAME did not affect embryonic survival or body mass of the embryos. The contractile responses to KCl, endothelin-1, the thromboxane A2 mimetic U46619, noradrenaline, and electrical-field stimulation were not affected by exposure to L-NAME. In contrast, in ovo L-NAME exposure reduced the sensitivity of pulmonary arteries to acetylcholine (pD2: 6.53 +/- 0.14 vs. 6.96 +/- 0.13; p < 0.05) and this effect was reversed by the NOS substrate L-arginine. Relaxations induced by sodium nitroprusside or forskolin were not altered by chronic L-NAME. Pulmonary vessel density was not different, but the percentage medial wall area of small pulmonary arteries (external diameter 10-50 microm) was slightly but significantly increased in the embryos exposed to L-NAME. In addition, hearts of L-NAME-exposed embryos showed an increase in right and left ventricular wall area. CONCLUSIONS: Chronic inhibition of NOS produced, in the chick embryo, impairment of endothelium-dependent relaxation, structural remodeling of the pulmonary vascular bed and biventricular cardiac enlargement.


Assuntos
Embrião de Galinha/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Coração/embriologia , Pulmão/embriologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Acetilcolina/farmacologia , Animais , Estimulação Elétrica , Endotelina-1/farmacologia , Coração/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Norepinefrina/farmacologia , Cloreto de Potássio/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/embriologia , Tromboxano A2/análogos & derivados , Fatores de Tempo
10.
Am J Respir Cell Mol Biol ; 26(1): 152-9, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11751215

RESUMO

Lipopolysaccharide (LPS), a major proinflammatory glycolipid component of the gram-negative bacterial cell wall, is one of the agents ubiquitously present as contaminant on airborne particles, including air pollution, organic dusts, and cigarette smoke. Chronic exposure to significant levels of LPS is reported to be associated with the development and/or progression of many types of lung diseases, including asthma, chronic bronchitis, and progressive irreversible airflow obstruction, that are all characterized by chronic inflammatory processes in the lung. In the present study, pathologic effects of long-term LPS exposure to the lung were investigated in detail. To this end, a murine model in which mice were exposed to repeated intratracheal instillation of Escherichia coli LPS was developed. We show that long-term LPS instillation in mice results in persistent chronic pulmonary inflammation, characterized by peribronchial and perivascular lymphocytic aggregates (CD4(+), CD8(+), and CD19(+)), parenchymal accumulation of macrophages and CD8(+) T cells, and altered cytokine expression. Furthermore, airway and alveolar alterations such as mucus cell metaplasia, airway wall thickening, and irreversible alveolar enlargement accompanied the chronic inflammatory response. Interestingly, the observed inflammatory and pathologic changes mimic changes observed in human subjects with chronic inflammatory lung diseases, especially chronic obstructive pulmonary disease (COPD), suggesting that this murine model could be applicable to dissect the role of inflammation in the pathogenesis of these disease conditions.


Assuntos
Inflamação , Lipopolissacarídeos/farmacologia , Pulmão/imunologia , Traqueia/metabolismo , Animais , Antígenos CD19/biossíntese , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Citocinas/biossíntese , Escherichia coli/metabolismo , Imuno-Histoquímica , Pulmão/patologia , Linfócitos/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Mucosa/metabolismo , Alvéolos Pulmonares/imunologia , Alvéolos Pulmonares/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo
11.
Am J Physiol Regul Integr Comp Physiol ; 287(3): R642-51, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15117730

RESUMO

Although chronic prenatal hypoxia is considered a major cause of persistent pulmonary hypertension of the newborn, experimental studies have failed to consistently find pulmonary hypertensive changes after chronic intrauterine hypoxia. We hypothesized that chronic prenatal hypoxia induces changes in the pulmonary vasculature of the chicken embryo. We analyzed pulmonary arterial reactivity and structure and heart morphology of chicken embryos maintained from days 6 to 19 of the 21-day incubation period under normoxic (21% O(2)) or hypoxic (15% O(2)) conditions. Hypoxia increased mortality (0.46 vs. 0.14; P < 0.01) and reduced the body mass of the surviving 19-day embryos (22.4 +/- 0.5 vs. 26.6 +/- 0.7 g; P < 0.01). A decrease in the response of the pulmonary artery to KCl was observed in the 19-day hypoxic embryos. The contractile responses to endothelin-1, the thromboxane A(2) mimetic U-46619, norepinephrine, and electrical-field stimulation were also reduced in a proportion similar to that observed for KCl-induced contractions. In contrast, no hypoxia-induced decrease of response to vasoconstrictors was observed in externally pipped 21-day embryos (incubated under normoxia for the last 2 days). Relaxations induced by ACh, sodium nitroprusside, or forskolin were unaffected by chronic hypoxia in the pulmonary artery, but femoral artery segments of 19-day hypoxic embryos were significantly less sensitive to ACh than arteries of control embryos [pD(2) (= -log EC(50)): 6.51 +/- 0.1 vs. 7.05 +/- 0.1, P < 0.01]. Pulmonary vessel density, percent wall area, and periarterial sympathetic nerve density were not different between control and hypoxic embryos. In contrast, hypoxic hearts showed an increase in right and left ventricular wall area and thickness. We conclude that, in the chicken embryo, chronic moderate hypoxia during incubation transiently reduced pulmonary arterial contractile reactivity, impaired endothelium-dependent relaxation of femoral but not pulmonary arteries, and induced biventricular cardiac hypertrophy.


Assuntos
Cardiomegalia/embriologia , Cardiomegalia/etiologia , Embrião de Galinha , Hipóxia/complicações , Hipóxia/embriologia , Artéria Pulmonar/embriologia , Vasoconstrição , Animais , Cardiomegalia/patologia , Doença Crônica , Endotélio Vascular/embriologia , Artéria Femoral/embriologia , Coração/embriologia , Hipóxia/patologia , Hipóxia/fisiopatologia , Miocárdio/patologia , Artéria Pulmonar/patologia , Vasodilatação
12.
J Magn Reson Imaging ; 20(1): 105-10, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15221815

RESUMO

PURPOSE: To investigate the performance of high-resolution T1-weighted (T1w) turbo field echo (TFE) magnetic resonance imaging (MRI) for the identification of the high-risk component intraplaque hemorrhage, which is described in the literature as a troublesome component to detect. MATERIALS AND METHODS: An MRI scan was performed preoperatively on 11 patients who underwent carotid endarterectomy because of symptomatic carotid disease with a stenosis larger than 70%. A commonly used double inversion recovery (DIR) T1w turbo spin echo (TSE) served as the T1w control for the T1w TFE pulse sequence. The MR images were matched slice by slice with histology, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the MR images were calculated. Additionally, two readers, who were blinded for the histological results, independently assessed the MR slices concerning the presence of intraplaque hemorrhage. RESULTS: More than 80% of the histological proven intraplaque hemorrhage could be detected using the TFE sequence with a high interobserver agreement (Kappa = 0.73). The TFE sequence proved to be superior to the TSE sequence concerning SNR and CNR, but also in the qualitative detection of intraplaque hemorrhage. The false positive TFE results contained fibrous tissue and were all located outside the main plaque area. CONCLUSION: The present study shows that in vivo high-resolution T1w TFE MRI can identify the high-risk component intraplaque hemorrhage with a high detection rate in patients with symptomatic carotid disease. Larger clinical trials are warranted to investigate whether this technique can identify patients at risk for an ischemic attack.


Assuntos
Arteriosclerose/patologia , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/patologia , Hemorragia/diagnóstico , Imageamento por Ressonância Magnética , Idoso , Arteriosclerose/complicações , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/cirurgia , Endarterectomia das Carótidas , Reações Falso-Positivas , Hemorragia/complicações , Hemorragia/patologia , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador
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