EBUS-TBNA in Extrathoracic Malignancies: Diagnostic and Prognostic Implications.

PURPOSE: In patients with extrathoracic malignancies (EM) the role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the assessment of abnormal mediastinal lymph nodes (MLN) is controversial. The aim of this study was to assess the diagnostic yield and prognostic significance of EBUS-TBNA in these patients. METHODS: Retrospective analysis of patients with EM and abnormal MLN detected by Computed Tomography (CT) and/or Positron Emission Tomography (PET). RESULTS: A total of 161 patients with EM and abnormal MLN were included (93 males, 58%). The most common EM was melanoma (19%) and gastrointestinal cancer (17%). Assessed lymph nodes were mediastinal in 70% of cases and hilar in 30%. The most frequently sampled lymph nodes were subcarinal (45%) and lower right paratracheal (21%). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EBUS-TBNA for the diagnosis of malignancy were 88%, 100%, 100% and 87%, respectively. These values were similar regardless the type of EM except for head and neck tumors where the NPV was particularly low (67%). The diagnosis of neoplastic involvement by EBUS-TBNA implied a worse prognosis in terms of overall survival (p < 0.02) and cancer-specific survival (p < 0.001). CONCLUSIONS: In patients with EM and abnormal MLN, EBUS-TBNA has a high diagnostic yield. However, the NPV decrease in patients with head and neck tumors. Neoplastic MLN detected by EBUS-TBNA has prognostic implications in these patients.

Mediastinitis focal con trombosis arterial pulmonar asociada tras EBUS-TBNA / Focal Mediastinitis and Pulmonary Arterial Thrombosis after EBUS-TBNA

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Is invasive mediastinal staging necessary in intermediate risk patients with negative PET/CT?

BACKGROUND: Tumor involvement of mediastinal lymph nodes is of high importance in non-small cell lung cancer (NSCLC). Invasive mediastinal staging is recommended in selected patients without evidence of mediastinal involvement on staging by imaging. In the present study we aimed to evaluate the effectiveness of invasive mediastinal staging in reducing pN2, its impact on survival and the risk factors for occult pN2. METHODS: Patients with NSCLC tumors larger than 3 cm, central tumors or cN1 cases treated in our institution between 2013 and 2018 were prospectively included in the study. Incidence of pN2 and overall survival was compared among invasively staged (IS) and non-invasively staged groups (NIS). Multivariate analysis was performed to identify risk factors of pN2. RESULTS: A total of 201 patients were included in the study, 79 (39.3%) of whom were not invasively staged (NIS group) and 122 (60.7%) were invasively staged (IS group). Incidence of cN1 and mean PET/CT uptake was different among both groups. Prevalence of pN2 was similar in both groups (7.6% in NIS vs. 12.6% in IS; P>0.05). Median survival in IS-pN2 patients was 11 months longer than in NIS-pN2 group (33.6 vs. 22.5 months; P=0.245). cN1 emerged as the only a risk factor for pN2. CONCLUSIONS: Invasive staging does not reduce the incidence of pN2. However, this finding could be biased because in our series cN1 patients were more often staged and cN1 has been detected as a risk factor for pN2. In addition patient better selection after invasive staging might have an impact on overall survival. To conclude, invasive mediastinal staging in intermediate risk patients for positive mediastinal nodes is justified.

Linfoepitelioma-like primario pulmonar en paciente no asiático / Primary Pulmonary Lymphoepithelioma-Like Carcinoma in a Non-Asian Patient

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Efficacy and safety of one-day offline extracorporeal photopheresis schedule processing one total blood volume for treating patients with graft-versus-host disease.

BACKGROUND: Extracorporeal photopheresis (ECP) has been increasingly used as a second-line therapy for graft-versus-host disease (GVHD) but there is no consensus regarding the best therapeutic schedule. STUDY DESIGN AND METHODS: Our offline ECP schedule for treating patients with GVHD was retrospectively reviewed. Patients with acute GVHD were treated on 2 days per week for the first 2 weeks, followed by 1 day per week for 2 more weeks. After the first month of treatment, patients received treatment 1 day every 2 weeks for a minimum of 16 ECP procedures. Patients with chronic GVHD were treated on 1 day per week for 4 weeks followed by 1 day every 2 weeks for a minimum of 14 ECP procedures. RESULTS: Our series comprises 21 (45%) patients with acute GVHD and 26 (55%) patients with chronic GVHD who received 667 ECP procedures. A median (interquartile range [IQR]) of 1.0 (1.0-1.12) total blood volume was processed. Patients with acute and chronic GVHD received ECP procedures during a median of 49 (IQR, 14-103) and 180 (IQR, 111-274) days, respectively. Mild citrate-induced symptoms were present in 98 (46%) and 232 (51%) procedures in patients with acute and chronic GVHD, respectively. Overall response rate (ORR) and overall survival (OS) were 57 and 38% (95% confidence interval [CI], 17%-59%), respectively, for patients with acute GVHD. For patients with chronic GVHD, ORR and OS were 77 and 61% (95% CI, 18%-87%), respectively. CONCLUSION: Our new offline ECP schedule for treating patients with acute and chronic GVHD was efficacious and safe.

Criobiopsia pulmonar y el principio KISS / Lung cryobiopsy and the KISS principle

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The Burden of Comorbidity and Complexity in Sarcoidosis: Impact of Associated Chronic Diseases.

PURPOSE: To evaluate comorbidity, complexity and poor outcomes in patients with sarcoidosis and to compare those scores with a control group. METHODS: 218 consecutive patients were diagnosed with sarcoidosis according to the ATS/ERS/WASOG criteria; extrathoracic involvement was evaluated using the 2014 WASOG organ assessment instrument. Sarcoidosis patients were compared with an age- and gender-matched control group of primary care outpatients without sarcoidosis. Comorbidities were assessed retrospectively using the Charlson Comorbidity Index (CCI); complexity was evaluated according to the classification into Clinical Risk Groups (CRG) and severity levels. RESULTS: The cohort included 142 women and 76 men; the mean age was 47.1 years at diagnosis of sarcoidosis and 55.9 years at the last visit. Patients with a CCI > 1 had a higher frequency of calcium/vitamin D abnormalities (p < 0.001), kidney involvement (p = 0.005) and a higher mortality rate (p < 0.001) compared with patients with a CCI ≤ 1. Patients with a CRG ≥ 6 had a higher frequency of extrathoracic involvement (p = 0.039), calcium/vitamin D abnormalities (p = 0.019) and treatment with glucocorticoids (p = 0.032) compared with patients with a CRG < 6. 11% patients died after a mean follow-up of 102.3 months. Country of birth, kidney involvement and extrathoracic disease were significantly associated with death. Patients with sarcoidosis had a higher frequency of liver (p < 0.001), pulmonary (p = 0.002) and autoimmune disease (p = 0.011) and cancer (p = 0.007) compared with the control group. CONCLUSION: We found higher rates of comorbidity and complexity in patients with sarcoidosis compared with a control group. Liver, pulmonary, autoimmune and neoplastic diseases were the main comorbidities found in patients with sarcoidosis.

Treatment with macrolides and glucocorticosteroids in severe community-acquired pneumonia: A post-hoc exploratory analysis of a randomized controlled trial.

BACKGROUND: Systemic corticosteroids have anti-inflammatory effects, whereas macrolides also have immunomodulatory activity in addition to their primary antimicrobial actions. We aimed to evaluate the potential interaction effect between corticosteroids and macrolides on the systemic inflammatory response in patients with severe community-acquired pneumonia to determine if combining these two immunomodulating agents was harmful, or possibly beneficial. METHODS: We performed a post-hoc exploratory analysis of a randomized clinical trial conducted in three tertiary hospitals in Spain. This trial included patients with severe community-acquired pneumonia with high inflammatory response (C-reactive protein [CRP] >15 mg/dL) who were randomized to receive methylprednisolone 0.5 mg/kg/tpd or placebo. The choice of antibiotic treatment was at the physician's discretion. One hundred and six patients were classified into four groups according to antimicrobial therapy combination (ß-lactam plus macrolide or ß-lactam plus fluoroquinolone) and corticosteroid arm (placebo or corticosteroids). The primary outcome was treatment failure (composite outcome of early treatment failure, or of late treatment failure, or of both early and late treatment failure). RESULTS: The methylprednisolone with ß-lactam plus macrolide group had more elderly patients, with comorbidities, and higher pneumonia severity index (PSI) risk class V, but a lower proportion of intensive care unit admission, compared to the other groups. We found non differences in treatment failure between groups (overall p = 0.374); however, a significant difference in late treatment failure was observed (4 patients in the placebo with ß-lactam plus macrolide group (31%) vs. 9 patients in the placebo with ß-lactam plus fluoroquinolone group (24%) vs. 0 patients in the methylprednisolone with ß-lactam plus macrolide group (0%) vs. 2 patients [5%] in the methylprednisolone with ß-lactam plus fluoroquinolone group overall p = 0.009). We found a significant difference for In-hospital mortality in the per protocol population (overall p = 0.01). We did not find significant differences in treatment failure, early or late; or In-hospital mortality after adjusting for severity (PSI), year and centre of enrolment. CONCLUSIONS: In this exploratory analysis, we observed that the glucocorticosteroids and macrolides combination had no statistically significant association with main clinical outcomes compared with other combinations in patients with severe community acquired pneumonia and a high inflammatory response after taking account potential confounders. TRIAL REGISTRATION: Clinicaltrials.gov NCT00908713.

Epidemiologic patterns of disease expression in sarcoidosis: age, gender and ethnicity-related differences.

OBJECTIVES: To evaluate the influence of age, gender and ethnicity in the clinical presentation of sarcoidosis in a cohort of Spanish patients. METHODS: We analysed 175 consecutive patients diagnosed with sarcoidosis between 1990 and 2014 in the Hospital Clinic of Barcelona, Spain. Sarcoidosis was diagnosed according to the 1999 WASOG criteria. Organ involvement was defined using the 2014 WASOG organ assessment instrument. RESULTS: There were 110 women and 65 men, with a mean age at diagnosis of 47.31 ± 15.46 years (range, 16-92); 23% of patients were born outside Spain. Women had a higher mean age (p=0.027), a higher frequency of cutaneous (OR=2.28) and musculoskeletal (OR=2.73) symptoms at diagnosis, and a lower frequency of cumulated WASOG involvements including renal involvement (OR=0.17), hypercalcaemia (OR=0.20) and raised ACE levels (OR=0.30). Patients aged ≥65 years had a lower frequency of cutaneous (OR=0.23) and musculoskeletal (OR=0.13) symptomatology at diagnosis and a higher frequency of cumulated WASOG involvements including renal involvement (OR=18.70) and calcium/vitamin D abnormalities (OR=5.31). According to ethnicity, non-Spanish-born patients had a lower mean age (40 vs. 49 years, p=0.001), a higher predominance of females (68% vs. 54%, p=0.036) and a higher frequency of radiographic stages I/II at diagnosis (97% vs. 78%, p=0.041) in comparison with Spanish-born patients. CONCLUSIONS: Using the new 2014 WASOG organ assessment instrument, we found that epidemiological features (age at diagnosis, gender and ethnicity) play a significant role in the presentation of sarcoidosis. Variations in these epidemiological features may aid early diagnostic suspicion, the search for histopathological confirmation and the prompt introduction of the appropriate therapy.

Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial.

IMPORTANCE: In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial. OBJECTIVE: To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150 mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012. INTERVENTIONS: Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission. MAIN OUTCOMES AND MEASURES: The primary outcome was treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortality was a secondary outcome and adverse events were assessed. RESULTS: There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) (P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, -6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group (P = .34). CONCLUSIONS AND RELEVANCE: Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00908713.

Endotracheal tubes for critically ill patients: an in vivo analysis of associated tracheal injury, mucociliary clearance, and sealing efficacy.

BACKGROUND: Improvements in the design of the endotracheal tube (ETT) have been achieved in recent years. We evaluated tracheal injury associated with ETTs with novel high-volume low-pressure (HVLP) cuffs and subglottic secretions aspiration (SSA) and the effects on mucociliary clearance (MCC). METHODS: Twenty-nine pigs were intubated with ETTs comprising cylindrical or tapered cuffs and made of polyvinylchloride (PVC) or polyurethane. In specific ETTs, SSA was performed every 2 h. Following 76 h of mechanical ventilation, pigs were weaned and extubated. Images of the tracheal wall were recorded before intubation, at extubation, and 24 and 96 h thereafter through a fluorescence bronchoscope. We calculated the red-to-green intensity ratio (R/G), an index of tracheal injury, and the green-plus-blue (G+B) intensity, an index of normalcy, of the most injured tracheal regions. MCC was assessed through fluoroscopic tracking of radiopaque markers. After 96 h from extubation, pigs were killed, and a pathologist scored injury. RESULTS: Cylindrical cuffs presented a smaller increase in R/G vs tapered cuffs (P = .011). Additionally, cuffs made of polyurethane produced a minor increase in R/G (P = .012) and less G+B intensity decline (P = .022) vs PVC cuffs. Particularly, a cuff made of polyurethane and with a smaller outer diameter outperformed all cuffs. SSA-related histologic injury ranged from cilia loss to subepithelial inflammation. MCC was 0.9 ± 1.8 and 0.4 ± 0.9 mm/min for polyurethane and PVC cuffs, respectively (P < .001). CONCLUSIONS: HVLP cuffs and SSA produce tracheal injury, and the recovery is incomplete up to 96 h following extubation. Small, cylindrical-shaped cuffs made of polyurethane cause less injury. MCC decline is reduced with polyurethane cuffs.

High smoking cessation rate in Crohn's disease patients after physician advice--the TABACROHN Study.

INTRODUCTION: Tobacco smoking has a significant impact on the development of Crohn's disease (CD) and its clinical course, making smoking cessation one of the main goals in CD therapeutic strategy. AIMS: To evaluate the effectiveness of an advice-based smoking cessation strategy among CD patients. METHODS: We have performed a prospective multicenter study which enrolled 408 CD smokers. At inclusion all patients were instructed about the risks of smoking and subsequently followed every 3 months. Each center used additional smoking cessation strategies based on available resources. Urinary cotinine and exhaled carbon monoxide levels were evaluated in a subgroup of patients. RESULTS: Median study follow up was 18 months. 31% of the patients achieved complete smoking cessation and 23% were smoking-free at the end of their follow up with 8% of smoking relapse. Most patients not achieving smoking cessation did not change their smoking habit with only 5% presenting a decrease in tobacco load. 63% of patients willing to quit smoking received help from another specialist, most frequently the pulmonologist (47%). Surprisingly, most patients (88%) tried to quit smoking with no pharmacological therapy and bupropion, varenicline and nicotine replacement treatment were used in few patients. Urinary cotinine and exhaled CO levels tested in a subgroup of patients proved to have a good correlation with the self-reported smoking habit. No predictors of successful smoking cessation were identified. CONCLUSION: Our results underline that an anti-tobacco strategy mostly based on CD patients's education and counseling is feasible and effective in helping patients reach complete abstinence.

Does smoking influence Crohn's disease in the biologic era? The TABACROHN study.

BACKGROUND: While most studies have found a negative effect of smoking on Crohn's disease (CD) phenotype, more recent data have failed to reproduce this association, which might be due to a current wider use of thiopurines and biologic therapy. The TABACROHN study aimed at defining the impact of smoking on CD in the largest published series. METHODS: This multicenter cross-sectional study included 1170 CD patients. Patients were classified as nonsmokers, current smokers, or former smokers according to their present smoking status. Clinical data regarding disease characteristics, treatment, and complications were collected. RESULTS: Smokers were more frequently under maintenance treatment when compared to nonsmokers. In addition, current smokers presented higher use of biologic drugs compared to nonsmokers. Tobacco exposure and a higher tobacco load were independent predictors of need for maintenance treatment and stenosing phenotype, respectively. CONCLUSIONS: In the era of early and widespread use of immunosuppressants and biologics, tobacco exposure is an independent predictor of need for maintenance treatment, specifically biologic therapy. The wider use of biologics and immunosuppressants could account for the existence of no major differences in disease behavior and complications between nonsmokers and current smokers.

Metástasis endobronquiales de carcinoma del canal anal / Endobronchial Metastases of Anal Canal Carcinoma

Las metástasis endobronquiales (MEB) de tumores primarios extratorácicos son infrecuentes. Los tumores de órganos sólidos que con más frecuencia se han asociado a MEB son el carcinoma de mama, el renal y el colorrectal. En esta nota clínica se describe el primer caso documentado de MEB de carcinoma del canal anal, neoplasia que constituye menos del 1% del total de tumores colorrectales. La presentación clínica de esta entidad es variable y es asintomática en más del 50% de los casos. Generalmente las MEB suelen diagnosticarse en fases avanzadas, por lo que la supervivencia es baja. Se trata pues de una manifestación clínica excepcional en que la broncoscopia tiene un importante papel tanto en el diagnóstico como en el tratamiento(AU)

Endobronchial metastases (EBM) secondary to extrapulmonary primary tumours are rare. The most common solid malignant tumours associated with EBM are breast, renal and colorectal carcinomas. This case report describes the first documented case of EBM from anal canal carcinoma. This neoplasm constitutes less than 1% of colorectal tumours. The clinical presentation of this entity is variable, being asymptomatic in more than 50% of cases. Generally, EBM are diagnosed in advanced stages and the survival after the diagnosis is poor. It is therefore an exceptional clinical manifestation in which bronchoscopy has an important role in the diagnosis and the treatment(AU)

Endobronchial metastases of anal canal carcinoma.

Endobronchial metastases (EBM) secondary to extrapulmonary primary tumours are rare. The most common solid malignant tumours associated with EBM are breast, renal and colorectal carcinomas. This case report describes the first documented case of EBM from anal canal carcinoma. This neoplasm constitutes less than 1% of colorectal tumours. The clinical presentation of this entity is variable, being asymptomatic in more than 50% of cases. Generally, EBM are diagnosed in advanced stages and the survival after the diagnosis is poor. It is therefore an exceptional clinical manifestation in which bronchoscopy has an important role in the diagnosis and the treatment.