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The predictive value of the extent of peri-operative lymph node (LN) sampling in relation to disease relapse in patients with pulmonary carcinoid (PC) is unknown. Furthermore, post-surgery follow-up recommendations rely on institutional retrospective studies with short follow-ups. We aimed to address these shortcomings by examining the relation between LN sampling and relapse in a population-based cohort with long-term follow-up. By combining the Dutch nationwide pathology and cancer registries, all patients with surgically resected PC (2003-2012) were included in this analysis (last update 2020). The extent of surgical LN dissection was scored for the number of LN samples, location (hilar/mediastinal), and completeness of resection according to European Society of Thoracic Surgeons (ESTS) guidelines. Relapse-free interval (RFI) was evaluated using Kaplan Meier and multivariate regression analysis. 662 patients were included. The median follow-up was 87.5 months. Relapse occurred in 10% of patients, mostly liver (51.8%) and locoregional sites (45%). The median RFI was 48.1 months (95% CI 36.8-59.4). Poor prognostic factors were atypical carcinoid, pN1/2, and R1/R2 resection. In 546 patients LN dissection data could be retrieved; at least one N2 LN was examined in 44% and completeness according to ESTS in merely 7%. In 477 cN0 patients, 5.9% had pN1 and 2.5% had pN2 disease. In conclusion, relapse occurred in 10% of PC patients with a median RFI of 48.1 months thereby underscoring the necessity of long-term follow-up. Extended mediastinal LN sampling was rarely performed but systematic nodal evaluation is recommended as it provides prognostic information on distant relapse.
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Tumor Carcinoide , Neoplasias Pulmonares , Linfonodos , Recidiva Local de Neoplasia , Humanos , Masculino , Feminino , Tumor Carcinoide/patologia , Tumor Carcinoide/cirurgia , Pessoa de Meia-Idade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Idoso , Recidiva Local de Neoplasia/patologia , Linfonodos/patologia , Linfonodos/cirurgia , Adulto , Excisão de Linfonodo , Metástase Linfática , Estudos Retrospectivos , PrognósticoRESUMO
Before initiating treatment of advanced non-small-cell lung cancer with tyrosine kinase inhibitors (eg, erlotinib, gefitinib, osimertinib, and afatinib), which inhibit the catalytic activity of epidermal growth factor receptor (EGFR), clinical guidelines require determining the EGFR mutational status for activating (EGFR exons 18, 19, 20, or 21) and resistance (EGFR exon 20) mutations. The EGFR resistance mutation T790M should be monitored at cancer progression. The Idylla EGFR Mutation Assay, performed on the Idylla molecular diagnostics platform, is a fully automated (<2.5 hours turnaround time) sample-to-result molecular test to qualitatively detect 51 EGFR oncogene point mutations, deletions, or insertions. In a 15-center evaluation, Idylla results on 449 archived formalin-fixed, paraffin-embedded tissue sections, originating from non-small-cell lung cancer biopsies and resection specimens, were compared with data obtained earlier with routine reference methods, including next-generation sequencing, Sanger sequencing, pyrosequencing, mass spectrometry, and PCR-based assays. When results were discordant, a third method of analysis was performed, when possible, to confirm test results. After confirmation testing and excluding invalids/errors and discordant results by design, a concordance of 97.6% was obtained between Idylla and routine test results. Even with <10 mm2 of tissue area, a valid Idylla result was obtained in 98.9% of the cases. The Idylla EGFR Mutation Assay enables sensitive detection of most relevant EGFR mutations in concordance with current guidelines, with minimal molecular expertise or infrastructure.
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Carcinoma Pulmonar de Células não Pequenas/genética , Análise Mutacional de DNA/métodos , Neoplasias Pulmonares/genética , Reação em Cadeia da Polimerase/métodos , Automação Laboratorial , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Formaldeído , Humanos , Neoplasias Pulmonares/patologia , Mutação , Inclusão em Parafina , Fixação de TecidosRESUMO
OBJECTIVES: To analyze the prevalence of high-risk HPV (human papillomavirus) and genetic alterations in nonmalignant tonsils. METHODS: We collected benign fresh tonsillar tissue specimens from 477 patients undergoing tonsillectomy because of chronic tonsillitis or tonsillar hypertrophy in 2012 (Group A, n=237) and in 2015 (Group B, n=240). Luminex xMAP technique served to detect E6/E7 DNA from 16 different high-risk HPV types. Tonsillar DNA and peripheral blood leukocyte DNA from the infected individuals were analyzed using Nimblegen SeqCap EZ Comprehensive Cancer Design panel. The panel targets 578 different genes that are relevant in carcinogenesis. HPV negative tonsillar specimens from age- and gender matched individuals were used as controls. All specimens harboring high-risk HPV were analyzed using fluorescence in situ hybridization (FISH). RESULTS: Five of 477 (1.0%) patients tested positive for the following HPV types: HPV16 (two cases), HPV52 (one case), HPV66 (one case), HPV52 and HPV68 (coinfection, one case). FISH analyses showed that the appearance of HPV in specimens infected with HPV 16 was episomal. Benign tonsils infected with high-risk HPV harbored mutations in EP300, NF1, PIK3CA, and RB1 which are considered relevant in the development of HPV-associated head and neck squamous cell carcinoma (SCC). CONCLUSIONS: The prevalence of high-risk HPV in nonmalignant tonsils is low. High-risk HPV positive tonsils harbored mutations in genes that are commonly altered in HPV-associated head and neck SCC. The role of these mutations in tonsillar carcinogenesis is an interesting target for future research.
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Mutação , Tonsila Palatina/metabolismo , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Papillomavirus Humano 16/isolamento & purificação , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Neoplasias Tonsilares/genética , Neoplasias Tonsilares/virologia , Adulto JovemRESUMO
AIMS: Currently pulmonary carcinoids are separated into typical and atypical based on mitotic count and presence of necrosis, according to the World Health Organization. At variance with gastroenteropancreatic neuroendocrine tumours, which are graded based on mitotic count and Ki-67 proliferative index, the use of Ki-67 for grading pulmonary carcinoids is still under debate. METHODS AND RESULTS: In this study we evaluated the prognostic impact of Ki-67 assessment in a multicentre cohort of 201 carcinoids [147 typical carcinoids (TCs) and 54 atypical carcinoids (ACs)] using manual analysis (2000 cells counted) and digital image analysis (in-house Leica Qwin program; ≥4500 cells counted). The Ki-67 proliferative index was correlated with overall survival by means of univariate analysis and in comparison to clinical data by means of multivariable analysis. The Ki-67 index was significantly higher in ACs than in TCs for both counting methods (P ≤ 2.7e-5 ). In addition, using cut-offs of 2.5% and 4% (manual counting) or 1% and 5% (digital analysis), the highest differences in overall survival were observed (P ≤ 0.0067). Nevertheless, histopathological classification into TCs and ACs showed an equally strong association with disease outcome, although Ki-67 had some additive value within TCs. Ki-67 index was not an independent predictor of survival in multivariable analysis. CONCLUSIONS: Our study demonstrates that, although Ki-67 is a strong prognostic factor for pulmonary carcinoids, its usefulness in addition to histopathology in prediction of prognosis is limited. None the less, it may have additional value, especially in cases that are difficult to classify, in combination with histopathology and other molecular markers.
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Tumor Carcinoide/mortalidade , Tumor Carcinoide/patologia , Antígeno Ki-67/análise , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/análise , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Organização Mundial da Saúde , Adulto JovemRESUMO
INTRODUCTION: Pulmonary neuroendocrine tumors (pNETs) are difficult to classify. We performed a population-based analysis to investigate the application of pNET nomenclature in daily pathology practice. METHODS: Conclusions from pathology reports (2003-2012) describing carcinoids, (large cell) neuroendocrine carcinomas (NECs), and carcinomas with neuroendocrine features/differentiation were retrieved from the Dutch Pathology Registry by queries on location and diagnosis and screened for terminology. Cases with a nonpulmonary or unknown origin and small cell lung cancer were excluded. Diagnoses were clustered into subgroups and the retrieved terminology was compared with the 2015 World Health Organization (WHO) diagnoses. By means of an online questionnaire, interpretation of the non-WHO nomenclature retrieved from pathology reports was evaluated (by 35 physicians and 19 pathologists). RESULTS: A total of 3216 unique pathology report conclusions with 55 different pNET diagnoses (n = 3052) and 20 uncertain diagnoses (n = 164) were analyzed. Non-WHO nomenclature was used in 15% of diagnoses (n = 488). Diagnoses could be clustered into carcinoids (n = 1086), NEC (n = 1316), carcinomas with neuroendocrine features/differentiation (n = 624), and unspecified pNETs (n = 26). Non-WHO nomenclature within these clusters was found for 7% of carcinoids, 20% of NECs, 13% of carcinomas with neuroendocrine features/differentiation, and 100% of unspecified pNETs and was observed more often in conclusions regarding biopsy or cytological specimens (62% and 12%) compared with resection specimens (26%). Analysis of the questionnaire results revealed that 4 of 19 diagnoses based on non-WHO nomenclature were uniformly interpreted (>50% agreement) by physicians, as were 10 of 19 diagnoses by pathologists. CONCLUSIONS: In 15% of pNETs other than small cell lung cancer, a non-WHO nomenclature diagnosis was provided, more frequently on the basis of smaller specimens. The interpretation was different between physicians and pathologists. Application of uniform nomenclature among all clinicians is advocated.
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Neoplasias Pulmonares/patologia , Oncologia/métodos , Tumores Neuroendócrinos/patologia , Patologia/métodos , Humanos , Estudos Retrospectivos , Inquéritos e Questionários , Terminologia como Assunto , Organização Mundial da SaúdeRESUMO
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is an orphan disease and few data are available on its clinical characteristics. Therefore, we analysed LCNEC registered in the Netherlands Cancer Registry, and compared data with small cell lung carcinoma (SCLC), squamous cell carcinoma (SqCC) and adenocarcinoma (AdC).Histologically confirmed LCNEC (n=952), SCLC (n=11â844), SqCC (n=19â633) and AdC (n=24â253) cases were selected from the Netherlands Cancer Registry (2003-2012). Patient characteristics, metastasis at diagnosis (2006 or later), overall survival (OS) including multivariate Cox models and first-line treatment were compared for stage I-II, III and IV disease.The number of LCNEC cases increased from 56 patients in 2003 to 143 in 2012, accounting for 0.9% of all lung cancers. Stage IV LCNEC patients (n=383) commonly had metastasis in the liver (47%), bone (32%) and brain (23%), resembling SCLC. Median OS (95% CI) of stage I-II, III and IV LCNEC patients was 32.4 (22.0-42.9), 12.6 (10.3-15.0) and 4.0 (3.5-4.6)â months, respectively. Multivariate-adjusted OS of LCNEC patients resembled that of SCLC patients, and was poorer than those of SqCC and AdC patients. However, frequency of surgical resection and adjuvant chemotherapy resembled SqCC and AdC more than SCLC.Diagnosis of LCNEC has increased in recent years. The metastatic pattern of LCNEC resembles SCLC as does the OS. However, early-stage treatment strategies seem more comparable to those of SqCC and AdC.
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Carcinoma de Células Grandes/patologia , Carcinoma Neuroendócrino/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/mortalidade , Carcinoma Neuroendócrino/mortalidade , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Países Baixos , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
OBJECTIVES: The purpose was to evaluate long-term outcome following balloon angioplasty for coarctation in adults. BACKGROUND: Long-term results of balloon angioplasty for native coarctation in adults remain incomplete, especially concerning the occurrence of aneurysm formation. METHODS: Long-term follow-up data were collected in consecutive patients retrospectively. Results of balloon angioplasty (29 patients, age 15-71 years, during 1995-2005) for discrete, native coarctation were evaluated, including MRI or CT. RESULTS: Mean follow-up ranged from 2.2 to 13 years (mean 8.5 +/- 3.2). Immediate success was obtained in all patients. Early mortality or complications were not encountered. Peak systolic pressure gradient decreased from 52 +/- 21 to 7.2 +/- 7.6 mm Hg (P < 0.001). Intima tear was detected in eight procedures angiographically, without signs of dissection. Three-month follow-up angiography in these patients showed unchanged (4/8 patients) or diminished abnormalities (4/8 patients). One asymptomatic patient, known with left ventricular dysfunction due to significant aortic valve insufficiency, died suddenly 5 years after balloon angioplasty. Recoarctation occurred in one patient (3%). Late aneurysm formation was excluded by MR in 24/29 and CT in remaining 5/29 patients during follow-up, including those patients in whom intima tear was encountered immediately postangioplasty. In three of seven patients an irregular aortic contour persisted, without indication of progression or aneurysm formation. Hypertension was completely relieved in 67% (14/21 patients) and improved in 33% (7/21 patients). CONCLUSIONS: Balloon angioplasty for native coarctation yields low reintervention probability in adult patients. Despite occurrence of angiographically established intimal tearing, aortic dissection and aneurysm formation were not encountered.
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Angioplastia com Balão/efeitos adversos , Aneurisma Aórtico/etiologia , Coartação Aórtica/terapia , Dissecção Aórtica/etiologia , Adolescente , Adulto , Idoso , Dissecção Aórtica/patologia , Angiografia Digital , Aneurisma Aórtico/patologia , Coartação Aórtica/complicações , Coartação Aórtica/patologia , Aortografia , Humanos , Hipertensão/etiologia , Hipertensão/terapia , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
Pleuropulmonary blastomas are rare malignant intrathoracic tumors of early childhood. They appear as a pulmonary- and/or pleural-based mass and their pathogenesis and relationship to other pediatric solid tumors is not well understood. In this study, paraffin-embedded material of five cases of pleuropulmonary blastoma was analyzed for genetic alterations by comparative genomic hybridization and five genetic loci by fluorescence in situ hybridization. Comparative genomic hybridization identified aberrations in all pleuropulmonary blastomas, including four amplifications in three tumors at chromosomes 5q33-34, 11q22.2-ter, 15q25-ter, and 19q11-13.2. The most frequent DNA gains involved 8q11-22.2 (four cases) and 20q (two cases), whereas the most common losses included 9p21-24 (two cases) and 11p14 (three cases). Chromosome 8 gains were confirmed by fluorescent in situ hybridization, resulting in the detection of up to five copies of chromosome 8 centromeres per nucleus. In the two surviving patients, chromosome 8 gains were the only genetic abnormality, suggesting that this might be an early event in pleuropulmonary blastoma carcinogenesis. The identification of new genetic alterations as well as the confirmation of previously reported ones (especially 8q gains) in pleuropulmonary blastoma should help to improve our understanding of both the molecular mechanisms underlying the tumorigenesis of pleuropulmonary blastoma and the relationship of pleuropulmonary blastoma with other pediatric tumors.
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Cromossomos Humanos Par 8/genética , Neoplasias Pulmonares/genética , Neoplasias Pleurais/genética , Blastoma Pulmonar/genética , Pré-Escolar , Aberrações Cromossômicas , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lactente , MasculinoRESUMO
The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 154-156, . The duplicate article has therefore been withdrawn.
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In situ hybridization (ISH) has significantly advanced the study of gene structure and expression in cells and tissues, but its application is often limited by detection sensitivity. The introduction of signal amplification after ISH using tyramides has greatly advanced in situ detection methods that also are now applicable in routine diagnostics. In this chapter, we provide detailed step-by-step protocols for synthesis of biotinylated tyramides, multiple-target deoxyribonucleic acid-ISH on cell preparations, both DNA- and messenger ribonucleic acid (mRNA)-ISH on formalin-fixed, paraffin-embedded tissue sections, and tyramide signal amplification for signal detection.
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Biotina/análogos & derivados , DNA/análise , Hibridização In Situ/métodos , Hibridização de Ácido Nucleico/métodos , RNA Mensageiro/análise , Tiramina/análogos & derivados , Animais , Biotina/metabolismo , Técnicas Histológicas , Humanos , Modelos Biológicos , Inclusão do Tecido , Fixação de Tecidos , Tiramina/metabolismoRESUMO
Percutaneous transvenous mitral balloon valvotomy (PTMV) has been proven to be an effective and safe method for treatment of patients with severe mitral valve stenosis. This technique has become an accepted alternative for surgical commissurotomy, not only in young patients with pliable valves, but also in selected older patients with extensive valvular pathology. This review highlights the significance of coexisting atrial fibrillation, patient selection and timing of PTMV in patients with mitral valve stenosis.
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Three female patients, a 22-year-old Moroccan woman, a 25-year-old Turkish woman and a 35-year-old Iraqi woman, became increasingly dyspnoeic during their pregnancy; this was a symptom of congestive heart failure due to mitral valve stenosis. Since all patients were refractory to medical treatment, they underwent invasive therapy by percutaneous transvenous mitral balloon valvotomy (PTMV). In two patients this therapy was successful, but in one patient a closed mitral valvotomy was needed. All three women delivered healthy infants, two immediately following the PTMV; at follow-up 2-4 years later, the women and infants were all doing well. The prevalence of mitral valve stenosis in the western world is increasing because of changing immigration patterns. When pregnant patients start complaining about dyspnoea, especially if they are immigrants, one should be aware of the possibility of mitral valve stenosis. PTMV is a safe and successful treatment for these patients and is preferred above surgical therapy because of its low morbidity and mortality for both mother and foetus. PTMV must be performed in a thoracic surgery centre by an experienced team and the X-ray exposure should be minimised.
Assuntos
Cateterismo , Dispneia/etiologia , Insuficiência Cardíaca/etiologia , Estenose da Valva Mitral/complicações , Complicações Cardiovasculares na Gravidez/etiologia , Adulto , Cateterismo/métodos , Dispneia/etnologia , Dispneia/terapia , Feminino , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/terapia , Humanos , Iraque/etnologia , Estenose da Valva Mitral/etnologia , Estenose da Valva Mitral/terapia , Marrocos/etnologia , Países Baixos , Gravidez , Complicações Cardiovasculares na Gravidez/etnologia , Complicações Cardiovasculares na Gravidez/terapia , Resultado da Gravidez , Turquia/etnologiaRESUMO
OBJECTIVE: To review the literature on the role of oncogenic human papillomaviruses (HPVs) in the carcinogenesis of the head and neck mucosa. MATERIAL AND METHODS: Molecular and epidemiological studies concerning the high-risk HPV types and their role in carcinogenesis in the head and neck region were screened. RESULTS: Different studies revealed that: (i) 15-25% of head and neck squamous cell carcinomas (HNSCCs) are clonally associated with high risk HPV types (type 16); (ii) the oropharynx and particularly the tonsils are the most susceptible sites; (iii) patients with HPV-positive tumours present with more advanced stages of disease, are relatively younger, do not have extravagant tobacco and alcohol intake and seem to have a better survival; (iv) HPV-positive tumours are characterized by poor differentiation grade and a basaloid appearance; and (v) HPV-positive tumours exhibit integrated HPV DNA, wild-type p53, pRb downregulation and overexpression of p16INK4A. CONCLUSION: Taken together, these data support the view that HPV-harbouring HNSCC can be considered a discrete tumour entity with, moreover, a favourable prognosis. Screening of patients, especially those with tonsillar cancers, for the presence of HPV may help to further optimize treatment protocols and to provide more accurate prognostic information.
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Carcinoma de Células Escamosas/virologia , Neoplasias Otorrinolaringológicas/virologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Cocarcinogênese , Humanos , Proteínas Oncogênicas Virais/análise , Neoplasias Otorrinolaringológicas/diagnóstico , Neoplasias Otorrinolaringológicas/genética , Neoplasias Otorrinolaringológicas/terapia , Papillomaviridae/isolamento & purificação , Prognóstico , Fatores de Risco , Fumar/efeitos adversos , Neoplasias Tonsilares/virologiaRESUMO
In the literature, it has been suggested that loss of the 10q25-26 region, including the DMBT1 gene (10q25.3), is correlated with initiation and/or malignant progression of astrocytomas, although the results of the studies on the loss of heterozygosity that led to this assumption are not unequivocal. For this reason, using double-target fluorescence in situ hybridization, we compared copy number changes of 10q25.3 to those of the pericentromeric region (10q12) in 10 cases each of astrocytoma grades II and IV. The same specimens were analyzed for copy number changes of chromosome 1, as a marker for polyploidy, and chromosome 7, which is often gained in astrocytomas of all grades. Our results show that selective loss of the 10q25.3 region was present in 2 of 10 specimens in both astrocytoma grade II and grade IV, occurring only in tumors with polysomy for 10q12. Furthermore, astrocytoma grade II often showed polyploidy for chromosomes 1, 7, and 10 (8 of 10 specimens). In addition, astrocytoma grade IV frequently exhibited losses of chromosome 10 in a high percentage of nuclei. Although based on a small number of cases, the results clearly show that loss of the 10q25.3 region is uncommon in astrocytoma grade II and mostly coincident with loss of chromosome 10 in grade IV tumors. These data indicate that selective loss of the 10q25.3 region, including the DMBT1 gene, is not an initiating event in the genesis of astrocytoma grade II.
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Aglutininas , Astrocitoma/genética , Neoplasias Encefálicas/genética , Cromossomos Humanos Par 10/genética , Glioblastoma/genética , Receptores de Superfície Celular/genética , Adulto , Idoso , Astrocitoma/química , Proteínas de Ligação ao Cálcio , Proteínas de Ligação a DNA , Feminino , Dosagem de Genes , Glioblastoma/química , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Proteínas Supressoras de TumorRESUMO
Multiple interactions with many different partners are responsible for the amazing functional versatility of proteins, especially those participating in cellular regulation. The structural properties that could facilitate multiple interactions are examined for small GTPases. The role of cellular constraints, compartmentation and scaffolds on protein-protein interactions is considered.
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GTP Fosfo-Hidrolases/química , GTP Fosfo-Hidrolases/metabolismo , Animais , Proteínas de Ligação ao GTP/metabolismo , Genes ras/fisiologia , Humanos , Modelos Moleculares , Peso Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-raf/fisiologia , Receptor Cross-Talk/fisiologia , Proteína ran de Ligação ao GTP/fisiologiaRESUMO
We describe a 34-year-old woman who had symptoms of heart failure due to an arteriovenous fistula between the right iliac artery and the inferior vena cava caused by surgery for a herniated intervertebral disk. The literature is reviewed. An intra-arterial placed covered stent was successfully used to close the fistula.
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BACKGROUND: According to the American College of Cardiology/American Heart Association guidelines, percutaneous coronary intervention (PCI) for left main coronary artery (LMCA) stenosis is contraindicated and coronary artery bypass graft surgery (CABG) is preferred. However, PCI of the LMCA is performed under exceptional circumstances. OBJECTIVE: To analyse the data of patients who underwent PCI of the unprotected LMCA in St Antonius Hospital, Nieuwegein, Netherlands. RESULTS: In a database of 17 683 PCI procedures, 71 patients (0.4%) were found with non-bifurcational LMCA stenosis who underwent an elective PCI between 1991 and 2001. Ages ranged from 26.7-86.5 years. Severe concomitant disease was the most frequent argument in favour of PCI instead of CABG. PCI consisted of only balloon angioplasty in 23 cases (32.4%). A stent was used in 46 cases (64.4%). Average follow up was 43 months (range 0-121 months). One patient died one day after the procedure. The total one year survival rate was 98.6% (70/71). Seven patients died during the follow up period, mostly because of non-cardiac reasons. The annual mortality rate was 2.5%. Recurrent elective percutaneous transluminal coronary angioplasty for restenosis of the LMCA was performed in one patient (1.4%) six weeks after the initial procedure. CABG was required in 13 patients (18.3%) throughout the follow up period. CONCLUSION: These results suggest that at highly experienced centres, elective PCI of the non-bifurcational LMCA can be performed safely where the anatomy is suitable.
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Angioplastia Coronária com Balão , Estenose Coronária/terapia , Guias de Prática Clínica como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/métodos , Contraindicações , Reestenose Coronária/etiologia , Estenose Coronária/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Retratamento , StentsRESUMO
Besides well-known risk factors such as tobacco use and alcohol consumption, oncogenic human papillomavirus (HPV) infection also has recently been suggested to promote head and neck tumorigenesis. HPV is known to cause cancer by inactivation of cell cycle regulators p53 and pRb via expression of viral oncoproteins E6 and E7. This indicates that p53 mutations are not a prerequisite in HPV-induced tumor development. However, discrepancy exists with respect to the frequency of head and neck squamous cell carcinomas (HNSCC) harboring DNA of oncogenic HPV and the fraction of these tumors showing p53 mutations. In our study, we examined the frequency of HNSCC demonstrating HPV 16/18 integration as identified by fluorescence in situ hybridization (FISH) and investigated their p53 (mutation) status by immunohistochemistry and single-strand conformation polymorphism (SSCP) analysis of exons 5-8. Paraffin-embedded, archival biopsy material from 27 premalignant mucosal lesions and 47 cases of HNSCC were analyzed. Ten of the 47 (21%) HNSCC unequivocally exhibited HPV 16 integration, including 8 of 12 (67%) tonsillar carcinomas. This is supported by the immunohistochemical detection of p16(INK4A) overexpression in all 10 HPV-positive tumors. Although FISH is considered to be less sensitive than PCR-based methods for HPV detection, our data clearly demonstrate clonal association of HPV with these tumors, as illustrated by the presence of integrated HPV 16 in both the primary tumor and their metastases in 2 patients. In contrast, HPV 16/18 DNA could not be detected in the premalignant lesions. In 30 of 47 (64%), HNSCC accumulation of p53 was observed, including 8 of the 10 HPV-positive carcinomas. However, in none of the latter cases could mutations in exons 5-8 be identified, except for a polymorphism in codon 213 of exon 6 in one patient. Evaluation of clinical data revealed a significant inverse relation between tobacco use with or without alcohol consumption, and HPV positivity of the tumors.