Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.

Inter-observer variance with the diagnosis of myelodysplastic syndromes (MDS) following the 2008 WHO classification.

Morphology is the basis of the diagnosis of myelodysplastic syndromes (MDS). The WHO classification offers prognostic information and helps with the treatment decisions. However, morphological changes are subject to potential inter-observer variance. The aim of our study was to explore the reliability of the 2008 WHO classification of MDS, reviewing 100 samples previously diagnosed with MDS using the 2001 WHO criteria. Specimens were collected from 10 hospitals and were evaluated by 10 morphologists, working in five pairs. Each observer evaluated 20 samples, and each sample was analyzed independently by two morphologists. The second observer was blinded to the clinical and laboratory data, except for the peripheral blood (PB) counts. Nineteen cases were considered as unclassified MDS (MDS-U) by the 2001 WHO classification, but only three remained as MDS-U by the 2008 WHO proposal. Discordance was observed in 26 of the 95 samples considered suitable (27 %). Although there were a high number of observers taking part, the rate of discordance was quite similar among the five pairs. The inter-observer concordance was very good regarding refractory anemia with excess blasts type 1 (RAEB-1) (10 of 12 cases, 84 %), RAEB-2 (nine of 10 cases, 90 %), and also good regarding refractory cytopenia with multilineage dysplasia (37 of 50 cases, 74 %). However, the categories with unilineage dysplasia were not reproducible in most of the cases. The rate of concordance with refractory cytopenia with unilineage dysplasia was 40 % (two of five cases) and 25 % with RA with ring sideroblasts (two of eight). Our results show that the 2008 WHO classification gives a more accurate stratification of MDS but also illustrates the difficulty in diagnosing MDS with unilineage dysplasia.

Hemotórax espontáneo como forma de presentación de carcinoma de pulmón / Spontaneous haemothorax as a form of presentation oflung cancer

El hemotórax espontáneo como forma de presentación de uncarcinoma de pulmón es extremadamente raro, siendo muy pocos los casos reflejados en la literatura. Hemos tenido la oportunidad de tratar a una paciente de 64 años, no fumadora, cuyo ingreso hospitalario fue debido a un hemotórax masivo izquierdo que estaba originado por un carcinoma de células gigantes en lóbulo inferior, como se comprobó en la intervención, y a la que se le pudo realizar una lobectomía inferior izquierda y linfadenectomía

Haemothorax as a form of presentation of lung cancer isextremely rare, and very few cases have been reported in the literature. We have had the opportunity to treat a 64 year old, nonsmoker patient, whose hospital admission was due to a massive left haemothorax that was originated by a giant cell carcinoma in the lower lobe and confirmed in the intervention. A left lower lobectomyand lymphadenectomy was completed

Hemotórax espontáneo como forma de presentación de carcinoma de pulmón / Spontaneous haemothoraz as a form of pesentation of lung cancer

El hemotórax espontáneo como forma de presentación de uncarcinoma de pulmón es extremadamente raro, siendo muy pocoslos casos reflejados en la literatura. Hemos tenido la oportunidadde tratar a una paciente de 64 años, no fumadora, cuyo ingresohospitalario fue debido a un hemotórax masivo izquierdo queestaba originado por un carcinoma de células gigantes en lóbuloinferior, como se comprobó en la intervención, y a la que se le pudorealizar una lobectomía inferior izquierda y linfadenectomía (AU)

Haemothorax as a form of presentation of lung cancer isextremely rare, and very few cases have been reported in the literature.We have had the opportunity to treat a 64 year old, nonsmokerpatient, whose hospital admission was due to a massive lefthaemothorax that was originated by a giant cell carcinoma in thelower lobe and confirmed in the intervention. A left lower lobectomyand lymphadenectomy was completed (AU)

Pulmonary embolism in a patient with severe congenital deficiency for factor V during treatment with fresh frozen plasma.

Thrombosis is a rare complication in patients with congenital clotting factor deficiencies. In most cases, it is related to inherited procoagulant factors, use of central venous catheters or administration of coagulation factor concentrates. There are only a few case reports about thrombotic events during treatment with fresh frozen plasma (FFP). We report the case of a patient with homozygous inherited factor V deficiency, who developed a pulmonary embolism at a time of treatment with methylene blue treated FFP (MBFFP). The patient had only two other factors predisposing to thrombosis and both were acquired: obesity and bed rest. He started anticoagulant treatment with low molecular weight heparin (LMWH) while the deficient factors were replaced with MBFFP. After 8 days of treatment the patient developed a severe respiratory insufficiency. Pulmonary haemorrhage was considered among the differential diagnosis and LMWH was stopped. An inferior vena cava filter was placed without any further thrombotic complications. To our knowledge, there are no reports about patients with clotting factor deficiencies who developed a thrombotic event during treatment with MBFFP.

Corrección del pectus excavatum por cirugía toracoscópica con la técnica de nuss / Correction of pectus excavatum with thoracoscopic surgery using the nuss technique

FUNDAMENTO: El pectus excavatum (PE) constituye ladeformación congénita más frecuente de la pared torácica, conimportantes consecuencias psicológicas y estéticas, además de funcionales.Hasta ahora la técnica más utilizada era la de Ravitch,consistente en la realización de condrectomías subpericóndricasbilaterales de los cartílagos afectos y osteotomías esternales transversalesy posterior estabilización.OBJETIVOS: Presentar nuestra experiencia en el tratamientoquirúrgico del pectus excavatum, siguiendo la técnica de correcciónmínimamente invasiva descrita por Nuss.MATERIALYMÉTODOS: A todos los pacientes se les realizóTAC de tórax con índices de Haller superiores a 3,25. Bajo anestesiageneral y mediante videotoracoscopia se colocó una barra estabilizadorasubesternal, realizando el abordaje mediante dos incisioneslaterales. Los extremos de la barra se fijaron medianteestabilizadores.RESULTADOS: Se trataron 11 pacientes (9 varones, 2 mujeres,rango de edad 10-31 años). El motivo de la intervención fue lacorrección estética. No se presentaron complicaciones intra ni postoperatoriasimportantes y no hubo ninguna muerte. El tiempooperatorio medio fue 58,6 min, el inicio de la deambulación mediafue 4,3 días y la estancia hospitalaria postoperatoria fue 7,2 días(tiempos menores que con la técnica de Ravitch). La complicaciónmás frecuente fue el dolor postoperatorio, bien controlado conanalgesia. Un paciente presentó intolerancia a la barra, siendonecesaria extraerla al año. En el 91% de nuestros casos se obtuvieronunos excelentes resultados estéticos.CONCLUSIONES: Consideramos que la técnica de Nussmínimamente invasiva debe de ser el procedimiento de elecciónpara corregir el pectus excavatum

THEORY: The pectus excavatum (PE) is the most frequentcongenital deformation of the thoracic wall, with major psychologicaland aesthetic, aside from functional, consequences. Until now,the Ravitch technique has been used, which consists of a bilateral,subperichondrial chondrectomy of the affected cartilage andtransverse, sternal osteotomy and subsequent stabilisation.OBJECTIVES: To present our experience in the surgicaltreatment of the pectus excavatum, using the minimally invasivecorrection technique described by Nuss.MATERIAL AND METHODS: A thoracic CAT-scan was performedon all the patients with a Haller indexes above to 3.25.Under general anaesthesia and using a video-thoracoscope, a stabilisingbar was placed under the sternum, approaching the areawith two lateral incisions. The ends of the bar were fixed with stabilisers.RESULTS: 11 patients were treated (9 men, 2 women, agerange 10-31 years of age). The intervention was carried out for aestheticreasons. There were no major complications during or afterthe intervention; there were no deaths. The average operating timewas 58.6 min; on average, patients were up within 4.3 days and thepostoperative hospital stay was 7.2 days (lower figures that withthe Ravitch technique). The most frequent complication was postoperativepain, which was well controlled with analgesics. Onepatient was unable to tolerate the bar; it had to be removed afterone year. In 91% of the cases excellent aesthetic results wereobtained.CONCLUSIONS:We consider that the Nuss technique is minimallyinvassive and should be the procedure of choice in the correctionof the pectus excavatum

[Video-assisted thoracoscopic thymectomy for the treatment of myasthenia gravis]. / Timectomía videotoracoscópica para el tratamiento de la miastenia gravis.

OBJECTIVE: Traditionally, thymectomy for myasthenia gravis has been performed using either a transcervical approach or a median sternotomy. However, excision of the thymic tissue by video-assisted thoracoscopic surgery is less aggressive and recovery is faster. The aim of this study was to evaluate the usefulness and outcomes of video-assisted thoracoscopic thymectomy. PATIENTS AND METHODS: Over the past 10 years, we have performed 25 video-assisted thoracoscopic thymectomies on patients with myasthenia gravis at our unit. This study included 16 women and 9 men, with a mean age of 48.1 years (range, 14-74 years). Right-side (22 cases) or left-side (3 cases) thoracoscopic surgery was performed, with a mean intervention time of 110 minutes (range, 60-193 minutes). RESULTS: No patient required assisted ventilation for more than 4 hours and the maximum stay in intensive care was less than 24 hours. Complications from surgery included 3 cases of contralateral pneumothorax, 1 pleural effusion, and 2 intraoperative hemorrhages from the thymic vein, all of which were resolved by video-assisted thoracoscopy. Likewise, 3 cases required conversion (due to hemorrhaging in 2 patients and technical difficulties in 1) and 2 required a second thoracoscopic intervention. No deaths occurred and clinical outcome was excellent in 11 cases (medical treatment no longer required), good in 10 (reduced medical treatment), and poor in 4 (no changes). CONCLUSIONS: Video-assisted thoracoscopic thymectomy is effective in the treatment of myasthenia gravis and improves patient recovery. In addition, the excellent surgical view allows the thymectomy to be performed with absolute safety.

[Video-assisted thoracoscopic surgery in 3 cases of adult cystic adenomatoid malformation]. / Tres casos de malformación adenomatoidea quística en el adulto tratados por cirugía videotoracoscópica.

Congenital cystic adenomatoid malformation involving the lung is a rare hamartomatous condition that is usually diagnosed in the neonatal period. The presentation of this malformation in older patients is exceptional and usually manifests in a series of recurrent lung infections affecting a single lobe or segment. The treatment of choice is complete surgical exeresis. This report of 3 cases of late presentation focuses on the surgical approach used and the unusual manifestation of recurrent spontaneous pneumothoraces in 1 patient. The patients were females aged 15, 16, and 25 years with histories of various respiratory diseases (extrinsic asthma, recurrent pneumonias, and pneumothoraces). The patients were referred to us for surgery with suspected diagnoses that were different from the final diagnoses in all cases. All underwent diagnostic video-assisted thoracoscopy to explore the affected hemothorax, and definitive treatment was possible during the procedure for 2 patients (a lobectomy and an atypical segmentectomy) by video-assisted surgery. The third patient underwent lobectomy by lateral thoracotomy after exploratory video-assisted thoracoscopy. Short- and long-term outcomes were excellent for all 3 patients.

[Giant solitary fibrous tumor of the pleura treated by video-assisted surgery: a case report]. / Tumor fibroso solitario gigante de pleura: un caso tratado por cirugía videoasistida.

Solitary fibrous tumors of the pleura are rare, with unpredictable clinical manifestations. By the time of diagnosis, the size and consistency of the tumor usually preclude the use of minimally invasive surgical techniques. We present a case of a 34-year-old male with a solitary fibrous tumor of the visceral pleura masquerading as a mediastinal tumor. The tumor was removed by video-assisted thoracic surgery.

Tratamiento de la hiperhidrosis palmar por simpatectomía torácica. Resultados inmediatos y calidad de vida postoperatoria / Thoracoscopic sympathectomy for palmar hyperhidrosis. Immediate results and postoperative quality of life

OBJETIVO: La hiperhidrosis palmar primaria localizada es un trastorno en la producción del sudor que resulta social y laboralmente incapacitante. El propósito de este estudio es evaluar los resultados, complicaciones y grado de satisfacción de los pacientes con hiperhidrosis palmar primaria tratados con simpatectomía videotoracoscópica T2-T3 bilateral en el Servicio de Cirugía General y Torácica del Hospital Universitario Virgen Macarena de Sevilla. MATERIAL Y MÉTODO: Se ha realizado un estudio clínico prospectivo histórico de 226 simpatectomías torácicas. La muestra la componen 113 pacientes (47 varones y 66 mujeres) de 14 a 50 años años de edad con hiperhidrosis palmar y axilar primaria, en algunos severa. A todos ellos se les intervino bajo anestesia general practicándoseles simpatectomía videotoracoscópica T2-T3 bilateral. Se presenta un seguimiento mediante cuestionario en relación con la calidad de vida y grado de satisfacción pre y postoperatoria. Se han efectuado análisis de frecuencia y descriptivos de los datos obtenidos sobre la técnica quirúrgica, calidad de vida y cambios posteriores a la cirugía y una prueba no paramétrica de Wilcoxon para dos variables relacionadas para contrastar diferencias significativas entre la calidad de vida pre y postoperatoria con relación a la hiperhidrosis y sus complicaciones. RESULTADOS: El porcentaje de éxito terapéutico ha sido del 100 por ciento. La tasa de complicaciones del procedimiento fue del 14,2 por ciento e incluyó hemotórax en dos pacientes, hemoneumotórax en tres, derrame pleural en dos y mínima cámara aérea apical en 9. De los 106 pacientes a los que se les realizó seguimiento entre 6 y 12 meses mediante entrevista y cuestionario, un 67 por ciento de ellos desarrollaron sudación compensatoria. Un 95 por ciento de estos pacientes refirió mejoría de su calidad de vida, y un 4 por ciento no experimentó ningún cambio en ella, sobre todo al considerar la aparición de la sudación compensatoria. El 97,2 por ciento de los pacientes entrevistados respondieron afirmativamente a la cuestión de si se volverían a operar. CONCLUSIÓN: La simpatectomía videotoracoscópica es un método efectivo para el tratamiento de la hiperhidrosis palmar primaria con bajas tasas de morbilidad y nulas de mortalidad. A pesar de la aparición de cambios posteriores como la sudación compensatoria, presenta una alta tasa de satisfacción y mejora de la calidad de vida de los pacientes (AU)

[Thoracoscopic sympathectomy for palmar hyperhidrosis. Immediate results and postoperative quality of life]. / Tratamiento de la hiperhidrosis palmar por simpatectomía torácica. Resultados inmediatos y calidad de vida postoperatoria.

OBJECTIVE: Primary palmar hyperhidrosis is a socially and occupationally debilitating disorder characterized by excessive sweating. The purpose of this study was to evaluate the results, complications, and degree of satisfaction among patients who underwent video-assisted bilateral thoracoscopic sympathectomy of the second and third ganglia (T2-T3) to treat primary palmar hyperhidrosis at the Department of General and Thoracic Surgery of the Hospital Universitario Virgen Macarena in Seville, Spain. MATERIAL AND METHOD: A study of 226 thoracoscopic sympathectomies was undertaken based on case histories and a prospective pre- and postoperative questionnaire survey. The sample was composed of 113 patients (47 males and 66 females), ranging in age from 14 to 50 years, with primary palmar and axillary hyperhidrosis, in some cases severe. Bilateral video-assisted thoracoscopic T2-T3 sympathectomy was performed under general anesthesia in all cases. Follow up included a questionnaire on pre- and postoperative quality of life and degree of satisfaction. Descriptive statistics on the surgical procedure, quality of life, and postoperative changes were compiled and frequency analyzed. A nonparametric Wilcoxon test for paired variables was performed to contrast significant differences between pre- and postoperative quality of life related to hyperhidrosis and its complications. RESULTS: The therapeutic success rate was 100%. Complications were seen in 14.2% of the cases and included hemothorax in two, hemopneumothorax in three, pleural hemorrhage in two, and minimal apical airspace in nine. Of the 106 patients who were monitored over a period of 6 to 12 months through follow-up interviews and questionnaires, 67% developed compensatory sweating, 95% reported improvement in quality of life, and 4% experienced no change in quality of life, mainly because of the emergence of compensatory sweating. Of the patients interviewed, 97.2% said that they would undergo the operation again. CONCLUSION: Video-assisted thoracoscopic sympathectomy for the treatment of primary palmar hyperhidrosis is effective, with low rates of morbidity and no mortality. Despite the appearance of postoperative changes such as compensatory sweating, patient satisfaction with the procedure is high and their quality of life improves.

Treatment of pulmonary sequestration by video-assisted thoracic surgery (VATS).

Pulmonary sequestration is a rare malformation of the respiratory tract that accounts for 0.15-6.4% of all congenital lung anomalies. Treatment requires resection of the lesion, provided that there is no technical contraindication. The lesion should first be evaluated using video thoracoscopy and then resected whenever possible by video-assisted thoracic surgery (VATS). We report a case of extralobar pulmonary sequestration in a 48-year-old woman. She underwent lobectomy by VATS and achieved an excellent outcome.

[Usefulness of video-assisted thoracoscopy for the diagnosis of solitary pulmonary nodules]. / Utilidad de la cirugía videotoracoscópica en el diagnóstico de los nódulos pulmonares solitarios.

OBJECTIVES: Various approaches are used for the diagnosis and treatment of solitary pulmonary nodules (SPN) of unknown origin. New imaging techniques and nuclear medicine have provided more information about SPN, but surgical removal is still the most sensitive and specific way to obtain a correct analysis of the lesion. With video-assisted thoracic surgery (VATS), a histological diagnosis can be obtained without resorting to thoracotomy. In the present study we describe our experience with the diagnosis and treatment of SPN using VATS. MATERIAL AND METHODS: From July 1992 through April 2001, 182 patients were operated on for SPN in our department. DESIGN: Retrospective study. Mean age: 59.2 years (12-78). Sex: 39 women and 143 men. Localization: Visual or instrumental exploration in 102 patients, with palpation in 52 cases and using a hookwire guided by preoperative computed tomography in 25 (with failure in 4 of those cases). Tissue was biopsied during surgery and when the lesion was malignant, oncological excision was performed during the same operation. RESULTS: A firm diagnosis was obtained by VATS for 178 patients (98.3%). For three other patients the surgeon had to take a needle biopsy (Tru-cut) during surgery, and in one case conversion to open surgery was necessary. Histopathology: hamartoma: 11; fibrous nodule: 10; bronchiolitis obliterans: 1; pneumoconiosis: 1; mesenchymal tumor: 3; inflammatory pseudotumor: 14; mucormycosis: 1; tuberculoma:17; lymphoma: 1; carcinoid tumor: 6; metastasis: 22; bronchogenic carcinoma: 95. Mortality was 0.55%, with 1 patient dying from massive pulmonary thromboembolism. Morbidity was 5%, from 9 minor complications. CONCLUSIONS: VATS is an effective approach, with low morbidity and mortality. We consider it to be the technique of choice for the diagnosis of all SPN and for the treatment of some, such as benign nodules and solitary metastases.

Utilidad de la cirugía videotoracoscópica en el diagnóstico de los nódulos pulmonares solitarios / Usefulness of video-assisted thoracoscopy for the diagnosis of solitary pulmonary nodules

OBJETIVOS: Varios tipos de estrategias se emplean para el diagnóstico y tratamiento de los nódulos pulmonares solitarios indeterminados (NPS). Las nuevas técnicas de imagen y de medicina nuclear parecen añadir más información a esta afección, pero aún es la exéresis quirúrgica el método más sensible y específico para obtener un correcto análisis de la lesión. Con la cirugía videotoracoscópica (CVT) se puede conseguir un diagnóstico histológico sin la necesidad de realizar una toracotomía. En este estudio se expone nuestra experiencia en el diagnóstico y tratamiento de los NPS con la CVT. MATERIAL Y MÉTODOS: Desde julio de 1992 a abril de 2001 se ha intervenido a 182 pacientes afectados de NPS en nuestro servicio. Diseño: estudio retrospectivo. Edad media: 59,2 años (límites, 12-78). Sexo: un total de 39 mujeres y 143 varones. Localización: exploración visual o instrumental en 102 pacientes, con palpación en 52 casos y con arpón guiado por tomografía computarizada (TC) preoperatoriamente en 25 (cuatro de ellos fallaron). A todos ellos se les realizó una biopsia intraoperatoria y cuando la lesión fue maligna se les practicó una exéresis oncológica en la misma operación. RESULTADOS: Se ha obtenido un diagnóstico de certeza, por CVT en 178 pacientes (98,3 per cent). En otros 3 pacientes fue necesario practicar biopsia con aguja Tru-cut® durante la CVT y un caso más hubo de convertirse a cirugía abierta. Histopatología: hamartoma, 11; nódulo fibroso, 10; bronquiolitis obliterante, 1; neumoconiosis, 1; tumor mesenquimal, 3; seudotumor inflamatorio, 14; mucormicosis, 1; tuberculoma, 17; linfoma, 1; tumor carcinoide, 6; metástasis, 22, y carcinoma broncogénico, 95. Mortalidad: 0,55 per cent, un paciente por tromboembolia pulmonar masiva. Morbilidad: 5 per cent, nueve complicaciones menores. CONCLUSIONES: La CVT es un abordaje muy efectivo, con baja morbilidad y mortalidad, y en nuestra opinión debe ser la técnica de elección para el diagnóstico de todos los NPS y el tratamiento de algunos, como los nódulos benignos y las metástasis solitarias (AU)

Cyclosporin A for the treatment of cytopenia associated with chronic lymphocytic leukemia.

BACKGROUND: Autoimmune cytopenias are a frequent complication in patients with chronic lymphocytic leukemia (CLL). Anecdotal reports suggest that cyclosporin A (CsA) may be beneficial for patients with CLL-associated pure red cell aplasia. In the current study, the authors investigated the use of CsA in the management of anemia or thrombocytopenia of presumed autoimmune etiology associated with CLL. METHODS: Thirty-one patients with CLL and anemia or thrombocytopenia of presumed autoimmune etiology were treated with CsA at a dose of 300 mg/day. Sixteen patients (52%) had anemia (hemoglobin or= 50 x 10(9)/L or an increase in hemoglobin >or= 3 g/dL. The median time to initial response was 3 weeks (range, 1-13 weeks) and the median time to best response was 10.5 weeks (range, 1-48 weeks). The median duration of response was 10 months (range, 1+-39+ months). Three patients with fludarabine-associated cytopenias were able to receive further therapy with fludarabine with a lesser decrease in the platelet count. A modest decrease in the tumor burden was observed in six patients. The most common toxicity was