Endobronchial metastasis from renal cell carcinoma as a reason for recurrent pulmonary infections

Endobronchial metastases (EBM) secondary to extrathoracic malignancies are very rare. Breast cancer, colorectal cancer andrenal cell carcinoma represent the most common types of cancer leading to endobronchial metastases. They usually representa late manifestation of other types of cancer and their prognosis is generally poor averaging a survival of 1-2 years in most caseseries. Due to their rarity, they remain a challenge for clinicians regarding whether they are primary lung tumors or not. This casereport article intends to present a case of a young man with a left nephrectomy due to clear cell renal carcinoma, who developedEBM 7 years later and to summarize available data in the field. Furthermore, the utility of diathermic snare as a treatment approachfor this entity is highlighted

Mελέτη ανοσολογικών μηχανισμών στην παθογένεια διάμεσων νοσημάτων του πνεύμονα

Εισαγωγή: O καρκίνος πνεύμονα φαίνεται να είναι συχνός σε ασθενείς με IPF, ωστόσο επί του παρόντος εκλείπουν από τη βιβλιογραφία μεγάλες βάσεις δεδομένων. Επιπρόσθετα, με βάση την υψηλή επίπτωση του καρκίνου στην IPF αλλά και με βάση το παράδειγμα repositioning του nintedanib, μελέτη ανοσολογικών μηχανισμών σχετικών με τον καρκίνο στην IPF μπορεί να έχει θετικά αποτελέσματα. Σκοπός: Να δημιουργήσουμε μία βάση δεδομένων για ασθενείς με IPF και καρκίνο πνεύμονα. Να μελετήσουμε προ-καρκινικά μονοπάτια στην IPF και συγκεκριμένα, 1) το ρόλο της SHP2 και 2) αν η λεμφαδενοπάθεια μεσοθωρακίου στην IPF αντικατοπτρίζει συγκεκριμένη ανοσολογική απόκριση και ειδικά αν παρατηρείται έκφραση των PD-1/PD-L1. Αποτελέσματα: Ταυτοποιήσαμε 324 ασθενείς με καρκίνο πνεύμονα μεταξύ 3178 ασθενών με IPF (10.2%). Δέκα έτη μετά τη διάγνωση της IPF, το 26.6% των εν ζωή ασθενών είχε καρκίνο πνεύμονα. Οι ασθενείς με IPF και καρκίνο πνεύμονα είχαν αυξημένο κίνδυνο θνητότητας σε σχέση με τους ασθενείς με IPF [HR: 1.51, (95% CI: 1.22 ως 1.86), p<0.0001]. Ασθενείς με IPF και καρκίνο πνεύμονα που έλαβαν αντι-ινωτική αγωγή [HR: 0.61, (95% CI: 0.42 ως 0.87), p=0.006] ή υπεβλήθησαν σε χειρουργική εξαίρεση του όγκου [πολυπαραγοντική ανάλυση-HR: 0.30 (95% CI: 0.11 ως 0.86), p=0.02] είχαν καλύτερη πρόγνωση σε σχέση με όσους δεν υπεβλήθησαν στην αντίστοιχη θεραπευτική αντιμετώπιση. Πνευμονικοί ινοβλάστες ποντικιών που έφεραν την D61G/+, η οποία καθιστά την SHP2 ενεργή, είχαν μειωμένο πολλαπλασιασμό (1.6-fold, p<0.05), μειωμένη μετανάστευση (2-fold, p<0.05) και επαγόμενη από τον TGFB-1 διαφοροποίηση σε μυοϊνοβλάστες σε σχέση με πνευμονικούς ινοβλάστες από wild-type ποντίκια. Αυξημένη % έκφραση του PD-1 παρατηρήθηκε στα λεμφοκύτταρα μεσοθωρακικών λεμφαδένων ασθενών με IPF συγκριτικά με την έκφραση σε ασθενείς με μη μικροκυτταρικό καρκίνο πνεύμονα. Υποτροπιδικοί λεμφαδένες ποντικιών που έλαβαν μπλεομυκίνη, είχαν αυξημένο μέγεθος και αυξημένη έκφραση PD-1 την ημέρα 14 σε σχέση τους λεμφαδένες ποντικιών που έλαβαν ορό. Το pembrolizumab εμφάνισε αντι-ινωτικές ιδιότητες με βάση το Ashcroft score και τη μηχανική της αναπνοής. Συμπέρασμα: Ο καρκίνος πνεύμονα είναι συχνός σε ασθενείς με IPF και έχει αρνητικό αντίκτυπο ως προς τη ζωή τους. Η μελέτη προκαρκινικών μονοπατιών στην IPF μπορεί να οδηγήσει σε σημαντικά ευρήματα. Η SHP2 και η αναστολή του PD-1 είχαν αντι-ινωτικές ιδιότητες και χρήζουν περαιτέρω διερεύνησης.Background: Lung cancer is prevalent in IPF, however there is still a lack of large databases. Given the prevalence of lung cancer in IPF and the paradigm of nintedanib repositioning, investigation of cancer-related pathways might have fruitful implications for patients with IPF. Aim/Methods: We aimed to create a registry for patients with IPF and lung cancer in Europe. Subsequently, we aimed to investigate cancer-related pathways in IPF. In particular, we investigated 1) the potential of SHP2 as anti-fibrotic mediator in vitro and 2) whether mediastinal lymphadenopathy in human and experimental lung fibrosis reflects specific immunologic activation and thus we focused on the expression of PD-1/PD-L1. Results: We identified 324 patients with lung cancer among 3178 patients with IPF (prevalence=10.2%). By the end of the 10 year-period following IPF diagnosis, 26.6% of alive patients with IPF had been diagnosed with lung cancer. Patients with IPF and lung cancer experienced increased risk of all-cause mortality than IPF patients without lung cancer [HR: 1.51, (95% CI: 1.22 to 1.86), p<0.0001]. Patients with IPF and lung cancer that received antifibrotics presented with decreased all cause-mortality compared to those who did not receive antifibrotics [HR: 0.61, (95% CI: 0.42 to 0.87), p=0.006]. In the adjusted model, a significantly lower proportion of surgically treated patients with IPF and otherwise technically operable lung cancer experienced all-cause mortality compared to non-surgically treated patients [HR: 0.30 (95% CI: 0.11 to 0.86), p=0.02]. Primary mouse lung fibroblasts derived from mice carrying a conditional knockin mutation (D61G/+), rendering SHP2 catalytic domain constitutively active, had reduced proliferation (1.6-fold, p<0.05), migration (2-fold, p<0.05), as well as reduced responsiveness of TGFB-1 induced fibroblasts to myofibroblasts differentiation, compared to wild-type ones. An increased median PD-1% expression in lymphocytes derived from mediastinal lymph nodes of patients with IPF compared to lung cancer was observed. Tracheobronchial lymph nodes isolated on day 14 from bleomycin-treated mice exhibited increased size and higher PD-1 mRNA levels compared to saline-treated animals. Pembrolizumab blunted bleomycin-induced lung fibrosis, as indicated by reduction in Ashcroft score and improvement in respiratory mechanics. Conclusion: Lung cancer exerts a dramatic impact on patients with IPF. Investigation of cancer-related pathways in pulmonary fibrosis yielded fruitful results, given thatSHP2 attenuated fibrotic responses and PD-1 inhibition might be a novel therapeutic target in IPF

Measles pneumonitis

Measles is an acute febrile illness, potentially fatal and highly contagious, which is transmitted through the respiratory mode. Fevercombined with one of the following: cough, coryza, conjunctivitis are the first manifestations of the disease. Koplik’s spots mayalso appear on the buccal mucosa providing an opportunity to set the diagnosis even before the emergence of rash. Rash typicallyappears 3–4 days after the onset of fever, initially on the face and behind the ears, and its appearance is associated with the peakof the symptoms. Measles affects multiple systems, including the respiratory system, with pneumonia being one of the most lethalcomplications. Management involves best supportive care, correction of dehydration and nutritional deficiencies, treatment ofsecondary bacterial infections and provision of vitamin A. Importantly, given that measles present with lifelong immunity followinginfection or vaccination, prevention through measles vaccination has a cardinal role for measles’ elimination. Indeed, public educationand vaccination led to an estimated 79% decrease in global measles deaths from 2000 to 2015. Nonetheless, the last two years haveseen a measles outbreak in several countries, partially due to the anti-vaccination movement. This article aims to present two casesof measles in our hospital and highlight the pressing need for vaccination in order to eradicate a potentially fatal disease

Przerzuty raka nerkowokomórkowego do oskrzeli przyczyną nawracających infekcji dróg oddechowych

Przerzuty do oskrzeli nowotworów rozwijających się poza klatką piersiową występują niezwykle rzadko. Najczęstszymi typami raka, które do nich prowadzą, są rak sutka, rak jelita grubego i rak nerkowokomórkowy. Przerzuty do oskrzeli stanowią zazwyczaj późny objaw innych typów nowotworu i ich rokowanie jest zazwyczaj złe — średnie przeżycie w większości przypadków wynosi 1–2 lata. Z powodu swojej unikatowości pozostają wyzwaniem dla lekarzy oceniających, czy są one pierwotnym guzem płuc, czy mają charakter wtórny. W niniejszym artykule przedstawiono przypadek młodego mężczyzny po usunięciu lewej nerki z powodu raka jasnokomórkowego, u którego po 7 latach pojawiły się przerzuty do oskrzeli, oraz podsumowano dostępne dane literaturowe. Autorzy odnoszą się ponadto do stosowania pętli diatermicznej jako metody leczenia tej jednostki chorobowej.Przerzuty do oskrzeli nowotworów rozwijających się poza klatką piersiową występują niezwykle rzadko. Najczęstszymi typami raka, które do nich prowadzą, są rak sutka, rak jelita grubego i rak nerkowokomórkowy. Przerzuty do oskrzeli stanowią zazwyczaj późny objaw innych typów nowotworu i ich rokowanie jest zazwyczaj złe — średnie przeżycie w większości przypadków wynosi 1–2 lata. Z powodu swojej unikatowości pozostają wyzwaniem dla lekarzy oceniających, czy są one pierwotnym guzem płuc, czy mają charakter wtórny. W niniejszym artykule przedstawiono przypadek młodego mężczyzny po usunięciu lewej nerki z powodu raka jasnokomórkowego, u którego po 7 latach pojawiły się przerzuty do oskrzeli, oraz podsumowano dostępne dane literaturowe. Autorzy odnoszą się ponadto do stosowania pętli diatermicznej jako metody leczenia tej jednostki chorobowej

Clinical improvement in Job syndrome following administration of co-trimoxazole, omalizumab and inhaled tobramycin

Established treatment regimens for the autosomal dominant hyperimmunoglobulin E syndrome, denominated Job syndrome, are lacking. Thus, Job syndrome still exerts a dramatic impact on patients’ quality of life. Our aim was to present safety and effectiveness of a regimen including co-trimoxazole, omalizumab and inhaled tobramycin in Job syndrome. A 26-year-old woman diagnosed with Job syndrome since infancy through sequencing revealing G342D mutation in STAT3 gene was initiated in the above mentioned treatment regimen; she was followed for 6 months, and to date, none recurrent pulmonary or skin infection was noticed. Furthermore, a considerable improvement in skin lesions was observed. A combination of anti-IgE and longitudinal use of inhaled antibiotics seems well-founded in Job syndrome

Biologic Treatments in Interstitial Lung Diseases

Interstitial lung diseases (ILD) represent a group of heterogeneous parenchymal lung disorders with complex pathophysiology, characterized by different clinical and radiological patterns, ultimately leading to pulmonary fibrosis. A considerable proportion of these disease entities present with no effective treatment, as current therapeutic regimens only slow down disease progression, thus leaving patients, at best case, with considerable functional disability. Biologic therapies have emerged and are being investigated in patients with different forms of ILD. Unfortunately, their safety profile has raised many concerns, as evidence shows that they might cause or exacerbate ILD status in a subgroup of patients. This review article aims to summarize the current state of knowledge on their role in patients with ILD and highlight future perspectives

Increased lipocalin-2 expression in pulmonary inflammation and fibrosis

IntroductionIdiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive interstitial lung disease with dismal prognosis. The underlying pathogenic mechanisms are poorly understood, resulting in a lack of effective treatments. However, recurrent epithelial damage is considered critical for disease initiation and perpetuation, via the secretion of soluble factors that amplify inflammation and lead to fibroblast activation and exuberant deposition of ECM components. Lipocalin-2 (LCN2) is a neutrophil gelatinase-associated lipocalin (NGAL) that has been suggested as a biomarker of kidney damage. LCN2 has been reported to modulate innate immunity, including the recruitment of neutrophils, and to protect against bacterial infections by sequestering iron.MethodsIn silico analysis of publicly available transcriptomic datasets; ELISAs on human IPF patients' bronchoalveolar lavage fluids (BALFs); bleomycin (BLM)-induced pulmonary inflammation and fibrosis and LPS-induced acute lung injury (ALI) in mice: pulmonary function tests, histology, Q-RT-PCR, western blot, and FACS analysis.Results and discussionIncreased LCN2 mRNA expression was detected in the lung tissue of IPF patients negatively correlating with respiratory functions, as also shown for BALF LCN2 protein levels in a cohort of IPF patients. Increased Lcn2 expression was also detected upon BLM-induced pulmonary inflammation and fibrosis, especially at the acute phase correlating with neutrophilic infiltration, as well as upon LPS-induced ALI, an animal model characterized by neutrophilic infiltration. Surprisingly, and non withstanding the limitations of the study and the observed trends, Lcn2−/− mice were found to still develop BLM- or LPS-induced pulmonary inflammation and fibrosis, thus questioning a major pathogenic role for Lcn2 in mice. However, LCN2 qualifies as a surrogate biomarker of pulmonary inflammation and a possible indicator of compromised pulmonary functions, urging for larger studies

The DIAMORFOSIS (DIAgnosis and Management Of lung canceR and FibrOSIS) survey. International survey and call for consensus

Background: Currently there is major lack of agreement on the diagnostic and therapeutic management of patients with idiopathic pulmonary fibrosis (IPF) and lung cancer. Our aim was to identify variations in diagnostic and management strategies across different institutions and provide rationale for a consensus statement on this issue. Methods: This was a joint-survey by European Respiratory Society (ERS) Assemblies 8, 11 and 12. The survey consisted of 25 questions. Results: Four hundred and ninety-four (n=494) physicians from 68 different countries and five continents responded to the survey. Ninety-four per cent of participants were pulmonologists, 1.8% thoracic surgeons and 1.9% oncologists; 97.7% were involved in multidisciplinary team approaches on diagnosis and management. Regular low-dose high-resolution computed tomography (HRCT) scan was used by 49.5% of the respondents to screen for lung cancer in IPF. Positron emission tomography (PET) scan and endobronchial ultrasound (EBUS) is performed by 60% and 88% to diagnose nodular lesions with mediastinal lymphadenopathy in patients with advanced and mild IPF, respectively. Eighty-three per cent of respondents continue anti-fibrotics following lung cancer diagnosis; safety precautions during surgical interventions including low tidal volume are applied by 67%. Stereotactic radiotherapy is used to treat patients with advanced IPF (diffusing capacity of the lung for carbon monoxide (D LCO) <35%) and otherwise operable nonsmall cell lung cancer (NSCLC) by 54% of respondents and doublet platinum regimens and immunotherapy for metastatic disease by 25% and 31.9%, respectively. Almost all participants (93%) replied that a consensus statement for the management of these patients is highly warranted. Conclusion: The diagnosis and management of IPF-lung cancer (LC) is heterogeneous with most respondents calling for a consensus statement