Self-expanding metallic Y-stent compared to silicone Y-stent for malignant lesions of the main carina: A single center retrospective study.

BACKGROUND: Bifurcation stents are often required in patients with malignant airway obstruction or fistulization involving the main carina. The silicone Y stent is the most used but remains challenging to place. The self-expanding metallic Y (SEM) stent appears easy to use. The objective is to report the feasibility, efficacy, and tolerance of SEM Y stent compared to silicone Y stent in patients with malignant tumors involving the main carina. PATIENTS AND METHODS: This retrospective single center study was performed between May 2004 and May 2017. All patients with malignant carina involvement treated with a bronchial Y stent were included. RESULTS: Forty silicone Y stents and 38 SEM Y stents were placed. Seven stenting placements failed in the silicone Y group but none in the SEM Y stent group (P=0.008). The median duration of the procedure was 80min (25-210) in the silicone Y group and.50min (25-110min) in the SEM Y group (P=0.001). There was no significant difference in terms of early or late complications between the 2 groups. Nine silicone Y stents (26.5%) and 7 SEM Y stents (18.4%) were removed (P=0.4). The median survival time following stent insertion was 171 days (Interquartile range (IQR): 53-379) in the silicone Y group and 104 days (IQR: 53-230) in the SEM Y group. CONCLUSION: If silicone Y stent remains the best solution for benign obstruction, SEM Y stent seems to be an easy alternative with no difference in terms of complication or ablation for malignant lesions involving the main carina.

Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial.

BACKGROUND: In 2013, the French National Cancer Institute initiated the AcSé program to provide patients with secure access to targeted therapies outside of their marketed approvals. Efficacy and safety was then assessed using a two-stage Simon phase II trial design. When the study design was designed, crizotinib was approved only as monotherapy for adults with anaplastic lymphoma kinase plus non-small-cell lung cancers (NSCLC). PATIENTS AND METHODS: Advanced NSCLC patients with c-MET ≥6 copies, c-MET-mutated, or ROS-1-translocated tumours were enrolled in one of the three cohorts. Patients were treated with crizotinib 250 mg twice daily. Efficacy was assessed using the objective response rate (ORR) after two cycles of crizotinib as primary outcome. Secondary outcomes included disease control rate at four cycles, best ORR, progression-free survival, overall survival, and drug tolerance. RESULTS: From August 2013 to March 2018, 5606 patients had their tumour tested for crizotinib targeted molecular alterations: 252 patients had c-MET ≥6 copies, 74 c-MET-mutation, and 78 ROS-1-translocated tumour. Finally, 25 patients in the c-MET ≥6 copies cohort, 28 in the c-MET-mutation cohort, and 37 in the ROS-1-translocation cohort were treated in the phase II trial. The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the mutated, and 47.2% in the ROS-1 cohort. The best ORR during treatment was 32% in the c-MET-≥6 copies cohort, 36% in the c-MET-mutated, and 69.4% in the ROS-1-translocation cohort. Safety data were consistent with that previously reported. CONCLUSIONS: Crizotinib activity in patients with ROS1-translocated tumours was confirmed. In the c-MET-mutation and c-MET ≥6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication. The continued targeting of c-MET with innovative therapies appears justified. CLINICAL TRIAL NUMBER: NCT02034981.

Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers.

OBJECTIVES: Procalcitonin (PCT) is widely used for the diagnosis of bacterial infections. The aim of this study was to evaluate PCT as a tumor and as a prognostic marker in patients with primary lung cancer. DESIGN AND METHODS: We retrospectively performed a PCT dosage in the frozen serum samples of 147 patients with pulmonary neoplasia for whom a test of neuron-specific enolase (NSE) had been conducted at the time of diagnosis. RESULTS: We show that a PCT serum level above 0.15 ng/mL was independently linked to the presence of a neuroendocrine component in the tumor (HR=5.809 95% CI [1.695-19.908] p: 0005). Thus, median PCT serum levels were significantly more elevated in small-cell lung cancers than in pulmonary adenocarcinomas: 0.33 ng/mL versus 0.07 ng/mL (p<0.001). However, the diagnostic value of serum PCT levels for diagnosing carcinoma with a neuroendocrine component remains low (sensitivity 63.8%; specificity 71.9%). In this series, serum PCT levels were significantly more elevated in the presence of liver metastases: 0.37 ng/mL versus 0.09 ng/mL in the absence of liver metastasis (p<0.001). In uni- and multivariate analyses, a serum PCT level above 0.15n g/mL and the presence of metastases and of sepsis at the time of diagnosis were independent factors of unfavorable prognosis. CONCLUSIONS: Serum PCT is elevated in patients with lung cancer with neuroendocrine component or with liver metastases. As a consequence, in this population, PCT has a poor specificity for bacterial infection. At diagnosis, an elevated serum PCT is an independent predictive factor of bad prognosis.

Randomized open-label non-comparative multicenter phase II trial of sequential erlotinib and docetaxel versus docetaxel alone in patients with non-small-cell lung cancer after failure of first-line chemotherapy: GFPC 10.02 study.

BACKGROUND: Concomitant administration of erlotinib with standard chemotherapy does not appear to improve survival among patients with non-small-cell lung cancer (NSCLC), but preliminary studies suggest that sequential administration might be effective. OBJECTIVE: To assess the efficacy and tolerability of second-line sequential administration of erlotinib and docetaxel in advanced NSCLC. METHODS: In an open-label phase II trial, patients with advanced NSCLC, EGFR wild-type or unknown, PS 0-2, in whom initial cisplatin-based chemotherapy had failed were randomized to sequential erlotinib 150 mg/d (day 2-16)+docetaxel (75 mg/m(2) d1) (arm ED) or docetaxel (75 mg/m(2) d1) alone (arm D) (21-day cycle). The primary endpoint was the progression-free survival rate at 15 weeks (PFS 15). Secondary endpoints included PFS, overall survival (OS), the overall response rate (ORR) and tolerability. Based on a Simon optimal two-stage design, the ED strategy was rejected if the primary endpoint was below 33/66 patients at the end of the two Simon stages. RESULTS: 147 patients were randomized (median age: 60±8 years, PS 0/1/2: 44/83/20 patients; males: 78%). The ED strategy was rejected, with only 18 of 73 patients achieving PFS15 in arm ED at the end of stage 2 and 17 of 74 patients in arm D. In arms ED and D, respectively, median PFS was 2.2 and 2.5 months and median OS was 6.5 and 8.3 months. CONCLUSION: Sequential erlotinib and docetaxel was not more effective than docetaxel alone as second-line treatment for advanced NSCLC with wild-type or unknown EGFR status.

Non-invasive evaluation of patients with viral hepatitis.

Liver fibrosis evaluation is essential in patients with chronic viral liver disease with major impact on treatment decisions. Liver biopsy is still considered the "gold-standard", but it is an invasive method, non-totally risk free, not very well accepted by patients, and unsuitable for regular follow-up examinations. In the last 10-15 years, several non-invasive methods for liver fibrosis assessment were developed: serological tests (simple or complex), ultrasound based elastographic methods (which can be classified in shear wave elastography methods and strain elastography methods) and magnetic resonance elastography. Today in clinical practice, ultrasound based elastographic methods are mostly used. From this category of methods, the oldest and more used is transient elastography, which was included also in several guidelines for assessing liver fibrosis in chronic hepatitis B and C patients. Each method has his advantages and weakness and today there is no consensus regarding which method should be considered the best "surrogate" for liver biopsy. Here we will try to give a comprehensive overview about the different techniques and depict the advantages and disadvantages of each of these methods.

Contrast-enhanced ultrasound (CEUS) for the evaluation of focal liver lesions - a prospective multicenter study of its usefulness in clinical practice.

PURPOSE: To assess the value of contrast-enhanced ultrasound (CEUS) for differentiating malignant from benign focal liver lesions (FLLs) and for diagnosing different FLL types. MATERIAL AND METHODS: CEUS performed in 14 Romanian centers was prospectively collected between February 2011 and June 2012. The inclusion criteria were: age > 18 years; patients diagnosed with 1 - 3 de novo FLLs on B-mode ultrasound; reference method (computed tomography (CT), magnetic resonance imaging (MRI) or biopsy) available; patient's informed consent. FLL lesions were characterized during CEUS according to the European Federation of Societies for Ultrasound in Medicine and Biology guidelines. For statistical analysis, indeterminate FLLs at CEUS were rated as false classifications. RESULTS: A total number of 536 cases were included in the final analysis, 344 malignant lesions (64.2 %) and 192 benign lesions (35.8 %). The reference method was: CT/MRI - 379 cases (70.7 %), pathological exam - 150 cases (27.9 %) and aspiration of liver abscesses - 7 cases (1.4 %). CEUS was conclusive in 89.3 % and inconclusive in 10.7 % of cases. To differentiate between malignant and benign FLLs, CEUS had 85.7 % sensitivity, 85.9 % specificity, 91.6 % positive predictive value, 77.1 % negative predictive value and 85.8 % accuracy. The CEUS accuracy for differentiation between malignant and benign liver lesions was similar in tumors with diameter ≤ 2 cm and those with diameter > 2 cm. CONCLUSION: CEUS represents a useful method in clinical practice for differentiating between malignant and benign FLLs detected on standard ultrasonography, and the results of this study are in concordance with previous multicenter studies: DEGUM (Germany) and STIC (France).

[Clomipramine hypersensitivity with predominantly pulmonary involvement]. / DRESS syndrome avec atteinte pulmonaire prédominante sous clomipramine.

Drug hypersensitivity (DRESS syndrome) is a rare disorder with diverse systemic and visceral manifestations. Pulmonary involvement is uncommon and is mainly characterized by eosinophilic infiltration. We report a case of DRESS syndrome induced by clomipramine with predominant pulmonary involvement.

A multicentre phase II randomised trial of weekly docetaxel/gemcitabine followed by erlotinib on progression, vs the reverse sequence, in elderly patients with advanced non small-cell lung cancer selected with a comprehensive geriatric assessment (the GFPC 0504 study).

BACKGROUND: Elderly cancer patients form a heterogeneous population in which therapeutic decision-making is often difficult. The aim of this randomised phase II trial was to evaluate the feasibility and activity of weekly docetaxel/gemcitabine (DG) followed by erlotinib after progression (arm A) vs erlotinib followed by DG after progression (arm B) in fit elderly patients with advanced non small-cell lung cancer (NSCLC). METHODS: Elderly chemotherapy-naive patients with stage IIIB/IV NSCLC were selected after a comprehensive geriatric assessment (socioeconomic, cognitive, depression, ADL and IADL assessments). The primary endpoint was the time to second progression (TTP2). Overall survival (OS), the time to first progression (TTP1) and safety were secondary endpoints. RESULTS: Between July 2006 and November 2008, 22 centres enrolled 100 patients. TTP2 was 7.5 and 5.8 months in arm A and arm B, respectively; TTP1 was 4.7 and 2.7 months; and the median OS time was 9.4 and 7.1 months; the respective 1-year survival rates were 36.2 and 31.4%. There was no major unexpected toxicity. CONCLUSION: These results suggest that weekly DG, followed by erlotinib, is a promising treatment for fit elderly patients with NSCLC; the efficacy of the reverse sequence was insufficient to recommend it for EGFR-non-selected patients.

Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: a multicenter phase II trial (GFPC 07-01).

BACKGROUND: Brain metastases (BM) occur in up to 40% of non-small-cell lung cancer (NSCLC) patients. This trial assessed the safety and efficacy of pemetrexed-cisplatin in this population. PATIENTS AND METHODS: Chemonaive NSCLC patients with BM ineligible for (radio)surgery, performance status (PS) of 0 to 2, were eligible for up to six cycles of cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) every 3 weeks. Whole -brain radiotherapy was given in case of disease progression or at chemotherapy completion. Primary end point was objective response rate (RR) on BM. Secondary end points included extracerebral and overall RR, safety profile and survival. RESULTS: Forty-three patients were enrolled. Initial characteristics were mean age 60.4 years; males 29; PS: 0 in 37.2%, 1 in 60.5% and 2 in 22.3% of patients; adenocarcinoma in 36 patients, large cell in 4 patients (nonsquamous, 93%) and squamous carcinoma in 3 patients. Functional classification of neurological status was stage I/II 86.0%, III 2.3% and IV 11.6%. Grade 3-4 hematological toxic effects were neutropenia, 11 patients (febrile neutropenia, 1 patient), and anemia, 6 patients. Non-hematological toxic effects were grade 2 urinary infection, one patient; grade 3 pneumonia, two patients; and grade 3 hypoacousia, one patient. Cerebral, extracerebral and overall RR by intent to treat analysis were 41.9%, 34.9% and 34.9%, respectively. Median survival time and time to progression were 7.4 and 4.0 months, respectively. CONCLUSION: Pemetrexed-cisplatin is an effective and well-tolerated regimen as first-line therapy for NSCLC patients with BM who always suffer a poor prognosis.

Thyroid stiffness assessment by acoustic radiation force impulse elastography (ARFI).

PURPOSE: To evaluate and compare the values of thyroid tissue elasticity in subjects without known thyroid pathology, in patients with Graves' disease and with chronic autoimmune thyroiditis (CAT). PATIENTS AND METHODS: We performed a prospective study that included 74 subjects, 23 without thyroid pathology, 29 with Graves' disease and 22 with CAT (diagnosed by specific tests). In all patients, 10 elastographic measurements were performed in the right thyroid lobe (RTL) and 10 in the left thyroid lobe (LTL) using a 2-6 MHz convex probe. Median values were calculated for each thyroid lobe, measured in meters/second (m/sec). We calculated a mean ARFI value from measurements made in the RTL and LTL. RESULTS: Thyroid stiffness was statistically significant lower in normal subjects vs. those with Graves' disease (2.07±0.44 m/sec vs. 2.82±0.47 m/sec, p<0.001) and with CAT (2.07±0.44 m/sec vs. 2.49±0.48 m/sec, p=0.004). We also found a statistically significant difference between subjects without thyroid pathology and those with autoimmune thyroid pathology (Graves' disease and CAT) (2.07±0.44 m/sec vs. 2.68±0.50 m/sec, p<0.001). CONCLUSION: ARFI seems to be a useful method for the evaluation of diffuse thyroid gland pathology and is able to predict with sufficient accuracy the presence of thyroid diffuse diseases (AUROC=0.80).

Double stenting of oesophagus and airways in palliative treatment of patients with oesophageal cancer is efficient but associated with a high morbidity.

BACKGROUND: Double stenting of oesophagus and airways may be required in palliative treatment of patients with locally advanced oesophageal cancer. AIM: To assess feasibility, efficacy and complications occurring in patients with locally advanced oesophageal cancer receiving both oesophagus and airways stenting. METHODS: In one single centre between 1997 and 2005, among 180 patients with locally advanced oesophageal cancer treated by the palliative placement of a self-expanding metal stent, patients requiring double stenting of oesophagus and airways were identified. Clinical efficacy, complications and survival were retrospectively collected. RESULTS: Fifteen patients (8.3% of 180) required a double stenting at follow-up. Symptomatic efficacy of oesophagus and airways stenting was 86.7% for dysphagia and 100% for dyspnoea. Median survival after the second stent insertion was 99 days. Life-threatening early complications occurred in three patients after double stenting (20%), including two deaths following oesophageal perforation and massive haemoptysis, respectively. Procedure-related mortality was 13.3%. CONCLUSIONS: Double stenting of oesophagus and airways is feasible in patients with locally advanced oesophageal cancer, with a relevant clinical efficacy. However, early major complications including procedure-related death may occur in as many as 20% of patients. This treatment should be reserved to very selected patients with severe symptoms and end-stage disease.

[Acute encephalopathy after infusion of paclitaxel]. / Encéphalopathie aiguë après injection de paclitaxel.

INTRODUCTION: Paclitaxel is an anti-neoplastic agent commonly used in the treatment of primary bronchial carcinoma and tumours of the breast and ovary. Its toxicity, haematological and peripheral neuropathy, are well known. On the other hand central nervous system toxicity is rare. CASE REPORT: We report a case of acute encephalopathy, occurring eight hours after infusion of Paclitaxel, in a patient treated for adenocarcinoma of the lung. It included drowsiness, confusion and hallucinations, and resolved completely after ten days. The diagnosis of encephalopathy secondary to Paclitaxel injection was reached after exclusion of other possible aetiologies. CONCLUSIONS: Acute encephalopathy is a rare complication of intravenous Paclitaxel treatment. The pathophysiology of this toxic effect is discussed: a direct toxicity of Paclitaxel or of its solvent (polyoxethylated castor oil), and the role of a pre-existing alteration of the blood-brain barrier.

Fatal haemoptysis in a case of lymphomatoid granulomatosis treated with rituximab.

Lymphomatoid granulomatosis is a rare angiocentric and angiodestructive disease, which commonly involves the lungs but also the brain, kidneys, liver and skin. This report describes the case of a 33-yr-old female with an aggressive form of lymphoid granulomatosis treated with an anti-CD20 antibody. Dramatic radiological improvement was seen at the fourth week. However, the patient died at home 1 month after the last rituximab administration from a massive haemoptysis.

[Diagnosis of lung cancer. Fluorescence bronchoscopy]. / Diagnostic des CBP. Les explorations endoscopiques respiratoires en fluorescence.

Autofluorescence endoscopy is used for more than ten years as an help to the diagnosis of bronchial precancerous lesions and early lung cancers. The technique has been extensively evaluated during the past decade including in two recent randomized studies versus conventional endoscopy that have shown an improvement for the localisation and the diagnosis of high grade precancerous lesions from 2 to 5 times. This paper reviews the principal applications and results of the use of autofluorescence endoscopy in high risk individuals, as well as innovative endoscopic approaches using the fluorescence properties of the respiratory tract.

Occupational and nonoccupational factors associated with high grade bronchial pre-invasive lesions.

Besides tobacco exposure, factors associated with the development of pre-invasive bronchial lesions are not known. Autofluorescence bronchoscopy was used to assess the prevalence of severe dysplasia and carcinoma in situ (SD/CIS) of the proximal bronchial tree in relation to occupational or nonoccupational carcinogen exposure. Among the 241 individuals in this study, the overall prevalence of at least one SD/CIS was 9% (21 subjects). Multivariable analysis revealed significant and independent associations between presence of SD/CIS and: 1) active smoking, relative to former smokers; 2) presence of synchronous invasive lung cancer; 3) duration of asbestos exposure and; 4) exposure to other occupational carcinogens. The independent associations of synchronous lung cancer with severe dysplasia and carcinoma, after adjusting for both occupational and nonoccupational carcinogen exposures, suggest other mechanisms than a field cancerisation may be involved in the carcinogenesis of these pre-invasive lesions. Moreover, active smokers, patients with recently resected invasive lung cancer and workers occupationally exposed to bronchial carcinogens may represent a population of choice for early cancer endoscopic detection programmes in view of their high severe dysplasia and carcinoma prevalence.

[Unrecognized causes of chronic cough]. / Causes méconnues de toux chronique.

Chronic cough is defined as persistence of the symptom for longer than one month. It is a common reason for consultation. A systematic diagnostic approach based on the history, clinical examination and a number of investigations (chest x-ray, lung function tests, oesophageal pH monitoring and sinus x-rays) reveals the cause in most cases. The main aetiologies are post-nasal drip, gastro-oesophageal reflex, asthma, chronic bronchitis, and the use of angiotensin converting enzyme inhibitors. Nevertheless, in some cases, the cause is not found. In this situation it is necessary to search for less common pathologies where cough is just a symptom of systemic disease, such as connective tissue disorder (Sjogren's syndrome, atrophic polychondritis), vasculitis (Wegener's granulomatosis), Horton's syndrome (cluster headaches), amyloidosis and inflammatory bowel disease. It may also be a matter of local pathology of the tracheo-bronchial tree, such as tracheo-bronchomegaly, tracheopathia osteoplastica, rare or unrecognized infections (whooping cough, post-viral cough, bronchial tuberculosis), reactive bronchial dysfunction, eosinophilic bronchitis or radiologically occult bronchial carcinoma. Il is also necessary to consider vocal cord dysfunction and cough due to medication before accepting a diagnosis of psychogenic cough.

Follow-up of bronchial precancerous lesions and carcinoma in situ using fluorescence endoscopy.

Little is known about the natural history of precancerous bronchial lesions. Histological changes occurring in 416 bronchial intraepithelial lesions (104 high-risk subjects) were assessed over a 2-yr period, using repeated follow-up autofluorescence endoscopies. During the study, 6 of 36 normal epitheliums became dysplastic; 47 of 152 metaplasia evolved to low-grade dysplasia, two progressed to carcinoma in situ, and one to invasive cancer; 6 of 169 low-grade epithelial lesions progressed to a persistent severe dysplasia; 10 of 27 severe dysplastic lesions and 28 of 32 carcinoma in situ persisted or progressed, respectively (p = 0.0005, severe dysplasia versus carcinoma in situ 24 mo outcome). Carcinoma in situ appeared more frequent in patients with a prior history or concomitant cancer (p = 0.003). Persistence of smoking during the study did not influence high-grade lesion outcome. Progression of low-grade epithelial lesions during the study occurred only in patients with at least a high-grade lesion in another site at baseline (9 of 147 lesions, 6.1%). Our study suggests that low-grade epithelial lesions could be safely followed-up at 2 yr in patients without high-grade lesions at baseline, whereas severe dysplasia should be treated if they persist at 3 mo. Immediate treatment of carcinoma in situ appears warranted.

Modalities of ventilation in obesity.

Obesity is nowadays the most frequently found health risk in the USA, where more than 1 in 3 adults have a weight > or = 20% over the ideal value. Obese patients are more prone to developing sleep apnoea syndrome and obesity hypoventilation syndrome as well as more frequent postoperative complications. Thus, acute and chronic respiratory failure episodes represent current presentations in clinical practice where noninvasive ventilation is very efficient and must be guided by polysomnographic data in order to decide on long-term respiratory treatment to avoid recurrence of acute on chronic decompensation.