Outcome and patterns of failure in testicular lymphoma: a multicenter Rare Cancer Network study.

PURPOSE: To assess the outcome and patterns of failure in patients with testicular lymphoma treated by chemotherapy (CT) and/or radiation therapy (RT). METHODS AND MATERIALS: Data from a series of 36 adult patients with Ann Arbor Stage I (n = 21), II (n = 9), III (n = 3), or IV (n = 3) primary testicular lymphoma, consecutively treated between 1980 and 1999, were collected in a retrospective multicenter study by the Rare Cancer Network. Median age was 64 years (range: 21-91 years). Full staging workup (chest X-ray, testicular ultrasound, abdominal ultrasound, and/or thoracoabdominal computer tomography, bone marrow assessment, full blood count, lactate dehydrogenase, and cerebrospinal fluid evaluation) was completed in 18 (50%) patients. All but one patient underwent orchidectomy, and spermatic cord infiltration was found in 9 patients. Most patients (n = 29) had CT, consisting in most cases of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with (n = 17) or without intrathecal CT. External RT was delivered to scrotum alone (n = 12) or testicular, iliac, and para-aortic regions (n = 8). The median RT dose was 31 Gy (range: 20-44 Gy) in a median of 17 fractions (10-24), using a median of 1.8 Gy (range: 1.5-2.5 Gy) per fraction. The median follow-up period was 42 months (range: 6-138 months). RESULTS: After a median period of 11 months (range: 1-76 months), 14 patients presented lymphoma progression, mostly in the central nervous system (CNS) (n = 8). Among the 17 patients who received intrathecal CT, 4 had a CNS relapse (p = NS). No testicular, iliac, or para-aortic relapse was observed in patients receiving RT to these regions. The 5-year overall, lymphoma-specific, and disease-free survival was 47%, 66%, and 43%, respectively. In univariate analyses, statistically significant factors favorably influencing the outcome were early-stage and combined modality treatment. Neither RT technique nor total dose influenced the outcome. Multivariate analysis revealed that the most favorable independent factors predicting the outcome were younger age, early-stage disease, and combined modality treatment. CONCLUSIONS: In this multicenter retrospective study, CNS was found to be the principal site of relapse, and no extra-CNS lymphoma progression was observed in the irradiated volumes. More effective CNS prophylaxis, including combined modalities, should be prospectively explored in this uncommon site of extranodal lymphoma.

Video-assisted right supradiaphragmatic thoracic duct ligation for non traumatic recurrent chylothorax

Introduction : Un chylothorax est une pathologie comprenant des manifestations respiratoires, nutritionnelles et immunologiques. La récidive du chylothorax ou l'échec du traitement conservateur imposent un traitement chirurgical. Ce travail rapporte notre expérience de ligature supra-diaphragmatique, vidéo-assistée du canal thoracique, pour chylothorax récurrent non traumatique. Patients et méthodes : Entre 1999 et 2004, nous avons recensé six observations (quatre du côté droit, un du côté gauche et un bilateral) Le chylothorax s'est développé chez trois patients traités par radio et chimiothérapie pour tumeur (deux lymphomes et une tumeur du sein) un dans le contexte d'une lymphangioléiomatose et un après greffe cardiaque. Résultats : Les patients ont bénéficié sous anesthésie générale, d'une ligature du canal thoracique supra-diaphragmatique, vidéo-assistée. Le temps opératoire moyen a été de 102 minutes. Le chylothorax a régressé chez cinq des six patients en sept jours. Un patient a été repris par thoracotomie droite au huitième jour pour chylothorax persistant. Dans la phase post-opératoire, un patient a développé une détresse respiratoire nécessitant une ventilation mécanique. Un autre patient a présenté un chylopéritoine important traité par un stent de Le Veen®. Le séjour moyen a été de quatorze jours sans mortalité péri-opératoire. Conclusion : Le traitement du chylothorax non traumatique récurrent est, en première intention, un traitement médical. En cas de récidive ou d'échec du traitement conservateur, le traitement chirurgical par ligature du canal thoracique supra- diaphragmatique, vidéo-assistée, permet de traiter avec succès le chylothorax récurrent non traumatique. -- Background: Chylothorax is an uncommon disorder with respiratory, nutritional and immunological manifestations. Surgical management is indicated in case of recurrence or failure after conservative treatment. We report our experience with video-assisted right-sided supradiaphrag¬matic thoracic duct ligation for non-traumatic, non-postoperative persistent or recurrent chylothorax. Patients and methods: The medical records of six patients operated at our institution between 1999 and 2004 were retrospectively reviewed. A right-sided chylothorax was found in four patients, a left-sided in one, and a bilateral in one. Three patients developed chylothorax after chemotherapy and chest irradiation for malignant diseases (lymphoma in two patients and breast cancer in one), one in the context of lymphangioleiomyomatosis, one due to a non-diagnosed lymphoma, and one after heart transplantation. Results: The mean operative time was 102 min, with an average length of hospital stay of 14 days. Persistent cessation of chylous effusion within 7 days after surgery was observed in 5/6 patients without recurrence during a mean follow-up time of 41 months. One patient with undiagnosed mediastinal lymphoma required re-operation and thoracic duct ligation on day 8 by right-sided thoracotomy due to persistent chylothorax. No 30-day mortality was recorded. Two patients presented postoperative complications including respiratory insufficiency requiring mechanical ventilation in one, and chylous ascites development requiring peritoneo-venous LeVeen shunting in one patient. Conclusions: Recurrent or persistent non-traumatic chylothorax may be successfully treated by video-assisted right supradiaphragmatic thoracic duct ligation.

Undocumented migrants in Switzerland: geographical origin versus legal status as risk factor for tuberculosis.

Undocumented migrants, meaning migrants without a legal residency permit, come to Geneva from countries with high tuberculosis (TB) incidence. We estimate here whether being undocumented is a determinant of TB, independently of origin. Cross-sectional study including undocumented migrants in a TB screening program in 2002; results were compared to 12,904 age and frequency matched participants in a general TB screening program conducted at various workplaces in Geneva, Switzerland from 1992 to 2002. A total of 206 undocumented migrants (36% male, 64% female, mean age 37.8 years (SD 11.8), 82.5% from Latin America) participated in the TB screening program. Compared to legal residents, undocumented migrants had an adjusted OR for TB-related fibrotic signs of 1.7 (95% CI 0.8;3.7). The OR of TB-related fibrotic signs for Latin American (vs. other) origin was 2.7 (95% CI 1.6;4.7) among legal residents and 5.5 (95% CI 2.8;10.8) among undocumented migrants. Chest X-ray screening identified a higher proportion of TB-related fibrotic signs among Latin Americans, independently of their residency status.

La prothèse de St Jude medical chez les patients âges de plus de 65 ans [St Jude's Medical prosthesis in patients over 65].

Between September 1979 and December 1982, 56 St Jude Medical valvular prostheses were implanted in 54 patients over 65 years of age. Surgery consisted in simple aortic valve replacement (35 cases), simple mitral valve replacement (12 cases), double aortic and mitral valve replacement (2 cases), valve replacement and coronary artery bypass surgery (3 cases), aortic valve replacement and replacement of the ascending aorta (1 case) and mitral valve replacement and tricuspid annuloplasty (1 case). The operative mortality (within 30 days of surgery) was 3.5% (2 cases). Patients were assessed by clinical examination, ECG, chest X-ray, echocardiogram and laboratory investigations on average 19 months after surgery. There were 3 late deaths (1 endocarditis, 1 cardiac failure and 1 subdural haematoma). No cases of significant haemolysis were observed. There were no cases of thrombosis of the valve or any deaths directly related to the valve. Four patients had cerebral embolism (4.9% per patient/year). None were fatal and only 1 patient had sequellae. Clinical improvement was very significant; 96% of the patients are now in the NYHA Classes I and II whilst 80% were in Class III or IV before surgery. The cardiothoracic ratio decreased significantly from 0.56 to 0.51 (p less than 0.01). The authors conclude that elderly patients may derive great benefits from valvular cardiac surgery and that age in itself is not a contraindication to this type of surgery. The St Jude Medical prosthesis is an excellent prosthesis but thromboembolism remains a major problem as with other mechanical prostheses. Anticoagulation for life is essential.

Which clinical signs predict hypoxaemia in young Senegalese children with acute lower respiratory tract disease?

BACKGROUND: Acute lower respiratory tract diseases are an important cause of mortality in children in resource-limited settings. In the absence of pulse oximetry, clinicians rely on clinical signs to detect hypoxaemia. OBJECTIVE: To assess the diagnostic value of clinical signs of hypoxaemia in children aged 2 months to 5 years with acute lower respiratory tract disease. METHODS: Seventy children with a history of cough and signs of respiratory distress were enrolled. Three experienced physicians recorded clinical signs and oxygen saturation by pulse oximetry. Hypoxaemia was defined as oxygen saturation <90%. Clinical predictors of hypoxaemia were evaluated using adjusted diagnostic odds ratios (aDOR). RESULTS: There was a 43% prevalence of hypoxaemia. An initial visual impression of poor general status [aDOR 20·0, 95% CI 3·8-106], severe chest-indrawing (aDOR 9·8, 95% CI 1·5-65), audible grunting (aDOR 6·9, 95% CI 1·4-25) and cyanosis (aDOR 26·5, 95% CI 1·1-677) were significant predictors of hypoxaemia. CONCLUSION: In children under 5 years of age, several simple clinical signs are reliable predictors of hypoxaemia. These should be included in diagnostic guidelines.

Is there a place for thoracoscopic debridement in the treatment of empyema in children?

BACKGROUND: Video-assisted thoracoscopic debridement has been shown to be a safe and efficient procedure for empyema in the adult patient. Its place in the management of childhood empyema remains controversial. METHODS: Over an 18-month period, 9 children were operated upon for pleural empyema. All children were initially treated with appropriate antibiotics and chest-tube drainage. Indication for surgery were persistent clinical symptoms and loculation of pleural fluid 5 to 7 days following initial treatment. In case of a duration of the illness of less than 14 days, an initial attempt was made to debride the pleural space by thoracoscopy. RESULTS: Mean duration of the illness prior to surgery was 15 days (range: 10-23 days), and mean duration of preoperative conservative treatment 10 days (range: 5-20 days). In five of the nine patients thoracoscopy was performed. In all patients thoracoscopy failed to provide adequate clearance of the diseased pleural space because of the advanced stage of the disease. The procedure was converted to a formal thoracotomy in four patients, the fifth patient continued to deteriorate and required formal thoracotomy and decortication seven days later. CONCLUSION: This limited experience suggests that, with the current management and indications, video-assisted thoracoscopic surgery adds little benefit to the treatment of childhood empyema.

Long-term sequelae in children surviving adult respiratory distress syndrome.

Nine children surviving severe adult respiratory distress syndrome were studied 0.9 to 4.2 years after the acute illness. They had received artificial ventilation for a mean of 9.4 days, with an Fio2 greater than 0.5 during a mean time of 34 hours and maximal positive end expiratory pressure levels in the range of 8 to 20 cm H2O. Three children had recurrent respiratory symptoms (moderate exertional dyspnea and cough), and two had evidence of fibrosis on chest radiographs. All patients had abnormal lung function; the most prominent findings were ventilation inequalities, as judged by real-time moment ratio analysis of multibreath nitrogen washout curves (abnormal in eight of nine patients) and hypoxemia (seven of nine). Lung volumes were less abnormal; one patient had restrictive and two had obstructive disease. A significant correlation between intensive care measures (Fio2 greater than 0.5 in hours and peak inspiratory plateau pressure) and lung function abnormalities (moment ratio analysis and hypoxemia) was found. A possibly increased susceptibility of the pediatric age group to the primary insult or respiratory therapy of adult respiratory distress syndrome is suggested.

Adaptive frequency tracking of the baseline ECG identifies the site of atrial fibrillation termination by catheter ablation

Multiple organization indices have been used to predict the outcome of stepwise catheter ablation in long-standing persistent atrial fibrillation (AF), however with limited success. Our study aims at developinginnovative organization indices from baseline ECG (i.e. during the procedure, before ablation) in orderto identify the site of AF termination by catheter ablation. Seventeen consecutive male patients (age60 ± 5 years, AF duration 7 ± 5 years) underwent a stepwise catheter ablation. Chest lead V6 was placedin the back (V6b). QRST cancelation was performed from chest leads V1 to V6b. Using an innovativeadaptive harmonic frequency tracking, two measures of AF organization were computed to quantify theharmonics components of ECG activity: (1) the adaptive phase difference variance (APD) between theAF harmonic components as a measure of AF regularity, and (2) and adaptive organization index (AOI)evaluating the cyclicity of the AF oscillations. Both adaptive indices were compared to indices computedusing a time-invariant approach: (1) ECG AF cycle length (AFCL), (2) the spectrum based organizationindex (OI), and (3) the time-invariant phase difference TIPD. Long-standing persistent AF was terminatedinto sinus rhythm or atrial tachycardia in 13/17 patients during stepwise ablation, 11 during left atriumablation (left terminated patients - LT), 2 during the right atrium ablation (right terminated patients -RT), and 4 were non terminated (NT) and required electrical cardioversion. Our findings showed that LTpatients were best separated from RT/NT before ablation by the duration of sustained AF and by AOI onchest lead V1 and APD from the dorsal lead V6b as compared to ECG AFCL, OI and TIPD, respectively. Ourresults suggest that adaptive measures of AF organization computed before ablation perform better thantime-invariant based indices for identifying patients whose AF will terminate during ablation within theleft atrium. These findings are indicative of a higher baseline organization in these patients that could beused to select candidates for the termination of AF by stepwise catheter ablation.© 2013 Elsevier Ltd. All rights reserved.

Développement, implémentation et utilisation pratique d'un score diagnostique [Development, implementation and practical use of a diagnostic score].

In recent years many clinical prediction rules (CPR) have been developed. Before a CPR can be used in clinical practice, different methodical steps are necessary, from the development of the score, the internal and external validation to the impact study. Before using a CPR in daily practice family doctors have to verify how the rules have been developed and whether this has been done in a population similar to the population in which they would use them. The aim of this paper is to describe the development of a CPR, and to discuss advantages and risks related to the use of CPR in order to help family doctors in their choice of scores for use in their daily practice.

High sensitivity of immature GABAergic neurons to blockers of voltage-gated calcium channels.

The involvement of voltage-gated calcium channels in the survival of immature CNS neurons was studied in aggregating brain cell cultures by examining cell type-specific effects of various channel blockers. Nifedipine (10 microM), a specific blocker of L-type calcium channels, caused a pronounced and irreversible decrease of glutamic acid decarboxylase activity, whereas the activity of choline acetyltransferase was significantly less affected. Flunarizine (1-10 microM, a relatively unspecific ion channel blocker) elicited similar effects, that were attenuated by NMDA. The glia-specific marker enzymes, glutamine synthetase and 2',3'-cyclic nucleotide 3'-phosphohydrolase, were affected only after treatment with high concentrations of nifedipine (50 microM) or NiCl2 (100 microM, shown to block T-type calcium channels). Nifedipine (50 microM), NiCl2 (100 microM), and flunarizine (5 microM) also caused a significant increase in the soluble nucleosome concentration, indicating increased apoptotic cell death. This effect was prevented by cycloheximide (1 microM). Furthermore, the combined treatment with calcicludine (10 nM, blocking L-type calcium channels) and funnel-web spider toxin-3.3 (100 nM, blocking T-type channels) also caused a significant increase in free nucleosomes as well as a decrease in glutamic acid decarboxylase activity. In contrast, cell viability was not affected by peptide blockers specific for N-, P-, and/or Q-type calcium channels. Highly differentiated cultures showed diminished susceptibility to nifedipine and flunarizine. The present data suggest that the survival of immature neurons, and particularly that of immature GABAergic neurons, requires the sustained entry of Ca2+ through voltage-gated calcium channels.

Impact of bedside open lung biopsies on the management of mechanically ventilated immunocompromised patients with acute respiratory distress syndrome of unknown etiology.

BACKGROUND: Open lung biopsy (OLB) is helpful in the management of patients with acute respiratory distress syndrome (ARDS) of unknown etiology. We determine the impact of surgical lung biopsies performed at the bedside on the management of patients with ARDS. METHODS: We reviewed all consecutive cases of patients with ARDS who underwent a surgical OLB at the bedside in a medical intensive care unit between 1993 and 2005. RESULTS: Biopsies were performed in 19 patients mechanically ventilated for ARDS of unknown etiology despite extensive diagnostic process and empirical therapeutic trials. Among them, 17 (89%) were immunocompromised and 10 patients experienced hematological malignancies. Surgical biopsies were obtained after a median (25%-75%) mechanical ventilation of 5 (2-11) days; mean (+/-SD) Pao(2)/Fio(2) ratio was 119.3 (+/-34.2) mm Hg. Histologic diagnoses were obtained in all cases and were specific in 13 patients (68%), including 9 (47%) not previously suspected. Immediate complications (26%) were local (pneumothorax, minimal bleeding) without general or respiratory consequences. The biopsy resulted in major changes in management in 17 patients (89%). It contributed to a decision to limit care in 12 of 17 patients who died. CONCLUSION: Our data confirm that surgical OLB may have an important impact on the management of patients with ARDS of unknown etiology after extensive diagnostic process. The procedure can be performed at the bedside, is safe, and has a high diagnostic yield leading to major changes in management, including withdrawal of vital support, in the majority of patients.

Heerfordt syndrome with unilateral facial nerve palsy: a rare presentation of sarcoidosis.

BACKGROUND: Heerfordt syndrome is rare and is characterized by fever, uveitis, parotid gland enlargement, and facial nerve palsy. We hereby present a case of Heerfordt syndrome with unilateral facial nerve palsy as a presentation of sarcoidosis. HISTORY AND SIGNS: A 29-year-old male patient from Sri Lanka presented with eye redness OU, blurred vision OD, fever, headache, night sweat, fatigue, and weight loss (5 kg over 1 month). Examination revealed mild anterior uveitis OU, mild vitritis OD, fundus whitish lesions OU, left otalgia, taste disorders, bilateral parotid gland enlargement, and left facial nerve palsy. Work-up for infection or tumour was negative. Chest computed tomography and transbronchial lymph node biopsy set the diagnosis of sarcoidosis. THERAPY AND OUTCOME: The patient recovered completely within 2 months under therapy with prednisone and azathioprine. One year after onset of treatment, no recurrence was noted. CONCLUSIONS: Heerfordt syndrome is a rare manifestation of neurosarcoidosis and has to be included in the differential diagnosis of facial nerve palsy.

Termination of Atrial Fibrillation by Catheter Ablation can be Successfully Predicted from Baseline ECG

Purpose Multiple organization indices (OIs) have been used to predict the outcome of stepwise catheter ablation (step-CA) in long-standing persistent AF (pers-AF), however with limited success. Our study aims at developing innovative OIs from baseline (BL, before ablation) ECG in order to predict the outcome of step-CA. Methods Fourteen consecutive patients (pts) (60±5 y, AF duration 21±9 m) underwent a step-CA consisting in pulmonary veins isolation, left atrial (LA) defragmentation and linear ablations, and right atrial (RA) ablations if non terminated. Chest lead V6 was placed in the back (V6b). After QRST cancellation from chest leads V1 to V6b, two OIs were computed to quantify the harmonic components of ECG atrial activity: 1) phase difference variance (PD) between the AF harmonic components as a measure of AF regularity, and 2) adaptive OI (AOI) evaluating the time evolution of the AF harmonic components. Both indices were compared to classical ones: a spectrum-based OI (SOI) and ECG AF cycle length (AFCL). Results Pers-AF was terminated into sinus rhythm or atrial tachycardia in 10/14 pts during step-CA, 8 during LA (LT), 2 during RA (RT) ablation, and 4 were non terminated (NT). The figure shows that LT was best separated from RT/NT before ablation by AOI computed on lead V1 (A) and PD from lead V6b (B) as compared to SOI and AFCL respectively. Conclusion Our results suggest that adaptive OIs computed before ablation perform better than classical OIs for separating LT from RT/NT pts. These findings are indicative of a higher baseline organization in LT pts that could be used to select candidates for the restoration of sinus rhythm by step-CA.

Outpatient treatment of pulmonary embolism

Pulmonary embolism (PE) is traditionally treated in hospital. Growing evidence from non randomized prospective studies suggests that a substantial proportion of patients with non-massive PE might be safely treated in the outpatient setting using low molecular weight heparins. Based on this evidence, professional societies started to recommend outpatient care for selected patients with non-massive PE. Despite these recommendations, outpatient treatment of non-massive PE appears to be uncommon in clinical practice. The major barriers to PE outpatient care are, firstly, the uncertainty as how to identify low risk patients with PE who are candidates for outpatient care and secondly the lack of high quality evidence from randomized trials demonstrating the safety of PE outpatient care compared to traditional inpatient management. Also, although clinical prognostic models, echocardiography and cardiac biomarkers accurately identify low risk patients with PE in prospective studies, the benefit of risk stratification strategies based on these instruments should be demonstrated in prospective management studies and clinical trials before they can be implemented as decision aids to guide PE outpatient treatment. Before high quality evidence documenting the safety of an outpatient treatment approach is published, outpatient management of non-massive PE cannot be generally recommended.

Respiratory nitric oxide and pulmonary artery pressure in children of aymara and European ancestry at high altitude.

Invasive studies suggest that healthy children living at high altitude display pulmonary hypertension, but the data to support this assumption are sparse. Nitric oxide (NO) synthesized by the respiratory epithelium regulates pulmonary artery pressure, and its synthesis was reported to be increased in Aymara high-altitude dwellers. We hypothesized that pulmonary artery pressure will be lower in Aymara children than in children of European ancestry at high altitude, and that this will be related to increased respiratory NO. We therefore compared pulmonary artery pressure and exhaled NO (a marker of respiratory epithelial NO synthesis) between large groups of healthy children of Aymara (n = 200; mean +/- SD age, 9.5 +/- 3.6 years) and European ancestry (n = 77) living at high altitude (3,600 to 4,000 m). We also studied a group of European children (n = 29) living at low altitude. The systolic right ventricular to right atrial pressure gradient in the Aymara children was normal, even though significantly higher than the gradient measured in European children at low altitude (22.5 +/- 6.1 mm Hg vs 17.7 +/- 3.1 mm Hg, p < 0.001). In children of European ancestry studied at high altitude, the pressure gradient was 33% higher than in the Aymara children (30.0 +/- 5.3 mm Hg vs 22.5 +/- 6.1 mm Hg, p < 0.0001). In contrast to what was expected, exhaled NO tended to be lower in Aymara children than in European children living at the same altitude (12.4 +/- 8.8 parts per billion [ppb] vs 16.1 +/- 11.1 ppb, p = 0.06) and was not related to pulmonary artery pressure in either group. Aymara children are protected from hypoxic pulmonary hypertension at high altitude. This protection does not appear to be related to increased respiratory NO synthesis.