RESUMEN
Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10(-11) for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS.
Asunto(s)
Proteínas de Unión al Calcio/genética , Cromosomas Humanos Par 20/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Proteínas de la Membrana/genética , Neoplasias de la Vejiga Urinaria/genética , Población Blanca/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Proteína Jagged-1 , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Proteínas Serrate-JaggedRESUMEN
Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
Asunto(s)
Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Proteínas de Transporte de Membrana/genética , Neoplasias de la Vejiga Urinaria/genética , Población Blanca/genética , Adulto , Anciano , Anciano de 80 o más Años , Cromosomas Humanos Par 18/genética , Progresión de la Enfermedad , Femenino , Sitios Genéticos/genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Reproducibilidad de los Resultados , Factores de Riesgo , Adulto Joven , Transportadores de UreaRESUMEN
OBJECTIVE: Radical nephroureterectomy is the standard treatment of organ-confined upper tract urothelial carcinoma (UTUC). The objective of this study was to investigate survival and bladder recurrence rate in Icelandic patients with UTUC who underwent radical nephroureterctomy (RNU) or other procedures with curative intent. MATERIAL AND METHODS: All patients who were diagnosed with UTUC in Iceland from 2003 to 2016 and treated with curative intent were included in the study. Information on patients was obtained retrospectively from patients' medical records and from the Icelandic Cause of Death Registry. RESULTS: Overall 63 patients underwent a procedure for UTUC with curative intent in Iceland during the study period. The median age was 71 years and the majority were male (65%). In 50 patients (79%), the tumor was a primary UTUC. The most common procedure was RNU (78%) and eight patients (13%) underwent a kidney-sparing procedure. No patient died within 90 d of surgery. Twenty-eight patients (44%) had pathological stage T2 or higher, whereas 35 patients (56%) had pathological stage T1 or lower. The median follow-up time was 98.8 months . During the follow-up time 25 patients (40%) were diagnosed with recurrence in the bladder. Five-year cancer-specific survival (CSS) was 67%. CONCLUSIONS: This population-based study shows that the oncologic outcome in Icelandic patients with UTUC is similar to what has been reported in other countries. Bladder recurrence rate is high and can hopefully be reduced by improvements in surgical and intravesical instillation treatment. Possibly more kidney-sparing surgeries could have been done during the study period; however, careful selection for those procedures is mandatory.
Asunto(s)
Carcinoma de Células Transicionales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Carcinoma de Células Transicionales/cirugía , Femenino , Humanos , Islandia/epidemiología , Masculino , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias Ureterales/cirugíaRESUMEN
Thymomas are usually benign tumors and are most often found in the anterior mediastinum. We report a rare case of a giant tumor in the right hemithorax that originated in the thymus. The tumor was 15x8 cm and histology revealed a type AB thymoma. The tumor was removed and the patient is doing well and is without symptoms two years after the operation. Key words: Thymoma, abdominal pain, giant tumor, mediastinum.
Asunto(s)
Timoma/patología , Neoplasias del Timo/patología , Anciano , Humanos , Timectomía , Timoma/cirugía , Neoplasias del Timo/cirugía , Resultado del Tratamiento , Carga TumoralRESUMEN
Pulmonary alveolar proteinosis (PAP) is a rare lung disease of unknown origin, where an amorphous lipoprotein material accumulates in the alveoli of the lungs. We describe a young male with a four month history of progressive dyspnea, low grade fever, hypoxemia and weight loss. Chest X-ray showed diffuse interstitial and alveolar infiltrates in both lungs. The diagnosis of PAP was confirmed with trans-bronchial lung biopsy. Because of a deteriorating clinical course a whole lung lavage was performed. Under general anesthesia, both lungs were lavaged with warm saline in two different sessions with good results. Two years later the patient is almost free of symptoms and lung function has markedly improved.
Asunto(s)
Proteinosis Alveolar Pulmonar , Biopsia , Lavado Broncoalveolar/métodos , Humanos , Masculino , Proteinosis Alveolar Pulmonar/diagnóstico , Proteinosis Alveolar Pulmonar/fisiopatología , Proteinosis Alveolar Pulmonar/terapia , Recuperación de la Función , Cloruro de Sodio/administración & dosificación , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
The objective of this study was to re-examine histologically and restage thymic epithelial tumours during a 25-year period and to correlate clinical and follow-up data. We utilized centralized registries in Iceland to establish a true nationwide incidence rate, previously unreported. A retrospective whole population study was carried out by including all patients diagnosed with a thymic epithelial tumour in Iceland between 1 January 1984 and 30 April 2010. Medical records were reviewed and presenting symptoms, diagnostic procedures and surgical outcome tabulated. The histology of all cases was reclassified according to the 2004 World Health Organization classification (A-TC). The Masaoka system was used for tumour staging. Median follow-up was 67 months. A total of 19 patients were identified, 11 men (58%) and 8 women, with mean age at presentation of 63 years (31-87 years). The age-standardized incidence rate (ASR) was 0.3 and 0.2/100 000/year for men and women, respectively. Types B2 (n = 5) and A (n = 5) were the most common histological subtypes. Half of the patients had local symptoms, and eight were diagnosed incidentally. Of 19 patients, 11 underwent resection of the tumour through median sternotomy. Five-year overall survival was 53%. All four patients with thymic carcinoma (TC) died of disease within 2 years of diagnosis. For the other 15 patients, no recurrences were reported. Thymic tumours are rare in Iceland with an ASR (w) of 0.28 per 100 000 a year. To our knowledge, these are the first nationwide ASR (w) figures reported. The prognosis for most thymic epithelial cell tumours is excellent. However, TCs have a dismal long-term survival.
Asunto(s)
Timoma/epidemiología , Timoma/patología , Neoplasias del Timo/epidemiología , Neoplasias del Timo/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Histocitoquímica , Humanos , Islandia/epidemiología , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10(-12)). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 x 10(-7)).
Asunto(s)
Cromosomas Humanos Par 8/genética , Predisposición Genética a la Enfermedad , Mutación/genética , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Estudios de Casos y Controles , Cromosomas Humanos Par 3/genética , Femenino , Marcadores Genéticos , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Persona de Mediana EdadRESUMEN
A young woman was admitted to Akranes Regional Hospital because of dyspnea, fatigue and fever. She was found to have bilateral pneumonia but etiology was not found. She was treated with antibiotics with good resolution and was discharged after eight days from the hospital. Four weeks later she noticed rapidly progressive dyspnea and was found to be hypoxemic, and to have restrictive spirometry and diffuse interstitial changes on chest radiography. Computerized tomography of the lungs showed diffuse ground glass changes. Transbronchial biopsies from the lungs showed numerous small granulomas. She was treated with prednisolone for a short time with excellent recovery. She stall-fed horses and underneath them was straw containing organic dust. This is important to keep in mind as a differential diagnosis to farmers lung disease that is caused by hay.