Lung cancer and concurrent or sequential lymphoma: Two case reports with hypersensitivity to bevacizumab and a review of the literature

Non-small cell lung cancer (NSCLC) accounts for ~80% of all cases of lung cancer, and is the leading cause of cancer-related mortality worldwide. The majority of NSCLC cases of are diagnosed at an advanced stage. The outcome of patients with advanced NSCLC is poor with a median survival time of ~12 months in European and American populations. Lymphoproliferative disorders (LPDs) represent a heterogeneous group of expanding lymphoid cells, which occurs as a result of immune dysfunction. LPDs are often associated with primary solid cancers. We report two cases of LPD diagnosed concurrently and successively to NSCLC. The first case presents a 65-year-old female patient with advanced IV stage lung cancer, according to the International Association for the Study of Lung Cancer TNM staging system. The patient developed a concurrent lymphoma and was treated with first-line therapy including six cycles of gemcitabine and cisplatin, however, the patient experienced an adverse drug reaction to bevacizumab, which was administered after gemcitabine and prior to cisplatin. The second case presented a 74-year-old male patient diagnosed with large B cell lymphoma. The patient acheived remission of the illness, however, after one year the patient was diagnosed with squamous cell lung cancer. After three years, the patient underwent surgery, however disease recurrence was identified. Subsequently, the patient was treated with sterotactic radiotherapy and oral chemotherapy. A review of the associated literature was also conducted.Non-small cell lung cancer (NSCLC) accounts for ~80% of all cases of lung cancer, and is the leading cause of cancer-related mortality worldwide. The majority of NSCLC cases of are diagnosed at an advanced stage. The outcome of patients with advanced NSCLC is poor with a median survival time of ~12 months in European and American populations. Lymphoproliferative disorders (LPDs) represent a heterogeneous group of expanding lymphoid cells, which occurs as a result of immune dysfunction. LPDs are often associated with primary solid cancers. We report two cases of LPD diagnosed concurrently and successively to NSCLC. The first case presents a 65-year-old female patient with advanced IV stage lung cancer, according to the International Association for the Study of Lung Cancer TNM staging system. The patient developed a concurrent lymphoma and was treated with first-line therapy including six cycles of gemcitabine and cisplatin, however, the patient experienced an adverse drug reaction to bevacizumab, which was administered after gemcitabine and prior to cisplatin. The second case presented a 74-year-old male patient diagnosed with large B cell lymphoma. The patient acheived remission of the illness, however, after one year the patient was diagnosed with squamous cell lung cancer. After three years, the patient underwent surgery, however disease recurrence was identified. Subsequently, the patient was treated with sterotactic radiotherapy and oral chemotherapy. A review of the associated literature was also conducte

Day and night control of COPD and role of pharmacotherapy: a review

The topic of 24-hour management of COPD is related to day-to-night symptoms management, specific follow-up and patients' adherence to therapy. COPD symptoms strongly vary during day and night, being worse in the night and early morning. This variability is not always adequately considered in the trials. Night-time symptoms are predictive of higher mortality and more frequent exacerbations; therefore, they should be a target of therapy. During night-time, in COPD patients the supine position is responsible for a different thoracic physiology; moreover, during some sleep phases the vagal stimulation determines increased bronchial secretions, increased blood flow in the bronchial circulation (enhancing inflammation) and increased airway resistance (broncho-motor tone). Moreover, in COPD patients the circadian rhythm may be impaired. The role of pharmacotherapy in this regard is still poorly investigated. Symptoms can be grossly differentiated according to the different phenotypes of the disease: wheezing recalls asthma, while dyspnea is strongly related to emphysema (dynamic hyperinflation) or obstructive bronchiolitis (secretions). Those symptoms may be different targets of therapy. In this regard, GOLD recommendations for the first time introduced the concept of phenotype distinction suggesting the use of inhaled corticosteroids (ICS) particularly when an asthmatic pattern or eosiophilic inflammations are present, and hypothesized different approaches to target symptoms (ie, dyspnea) or exacerbations. Pharmacotherapy should be evaluated and possibly directed on the basis of circadian variations, for instance, supporting the use of twice-daily rapid-action bronchodilators and evening dose of ICS. Recommendations on day and night symptoms monitoring strategies and choice of the specific drug according to patient's profile are still not systematically investigated or established. This review is the summary of an advisory board on the topic "24-hour control of COPD and role of pharmacotherapy", held by five pulmonologists, experts in respiratory pathophysiology, pharmacology and sleep medicine

Beclomethasone/Formoterol in Extra-Fine Formulation Improves Small Airway Dysfunction in COPD Patients

INTRODUCTION: In patients with chronic obstructive pulmonary disease (COPD), small airway dysfunction (SAD) is a key element and a functional consequence of the pathology. The exact role of SAD as a specific 'pharmacological target' represents an important research topic. Our objective was to ascertain whether an extra-fine formulation of beclomethasone dipropionate/formoterol fumarate (BDP/FF) NEXThaler 100/6mug b.i.d. could improve SAD and, consequently, the quality of life of COPD patients.METHODS: We enrolled COPD patients with severe airflow obstruction and at least one moderate exacerbation in the previous year, having started treatment with BDP/FF NEXThaler for no more than 1 week. Patients underwent three visits: at the start of the treatment (V1), 6 weeks (V2), and 12weeks later (V3). At each visit, we evaluated the fall in resistance from 5 to 20Hz (R5-R20) and residual volume/total lung capacity (RV/TLC) ratio by impulse oscillometry, spirometry, and plethysmography. The COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) questionnaire were also administered to assess the disease's impact on quality of life.RESULTS: We enrolled 43 COPD patients (mean age 69years, FEV1 43%). R5-R20 significantly changed from baseline [0.23±0.09kPa/(l/s)] to V2 [0.16±0.09kPa/(l/s)] and V3 [0.16±0.08kPa/(l/s)] (p<0.05). Clinical status was also significantly improved compared to baseline; in fact, CAT score changed from an average baseline value of 13-6 and 4 (V2 and V3, respectively) (p<0.05). A correlation was found between CAT percentage change values and the corresponding ones of R5-R20 (r=- 0.329, p=0.045) and RV/TLC (r=0.354, p=0.029).CONCLUSIONS: In COPD patients, treatment with BDP/FF extra-fine formulation improved functional parameters related to small airway disease as well as the disease impact on health status.TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04421742

Narrarsi ai tempi del COVID-19

Fondazione ISTUD, in collaborazione con Chiesi Italia, partendo dalla comprensione dei bisogni dei principali protagonisti della filiera della salute, pazienti, familiari, professionisti sanitari, societ\ue0 scientifiche, associazioni dei pazienti, istituzioni del mondo della salute e aziende delle life sciences, si pone l\u2019obiettivo di migliorare i percorsi di cura e assistenza, facilitando una sanit\ue0 sostenibile in grado di fornire risposte concrete nelle organizzazioni sanitarie. Nella realizzazione di questo Progetto di Ricerca partecipano, inoltre, professionisti provenienti dalle societ\ue0 scientifiche nel campo della pneumologia (AIPO, Associazione Italiana Pneumologi Ospedalieri; SIP/IRS, Societ\ue0 Italiana di Pneumologia/Italian Respiratory Society), della medicina generale (SIMG, Societ\ue0 Italiana di Medicina Generale; FIMMG, Federazione italiana Medici di Medicina Generale) e le Associazioni dei pazienti affetti da malattie respiratorie croniche (Associazione Italiana Pazienti BPCO, FederAsma e Allergie ODV). In quest\u2019atmosfera, nasce \u201cNARRARSI AI TEMPI DEL COVID-19 - Brevi diari di pazienti con BroncoPneumopatia Cronica Ostruttiva (BPCO), di loro familiari, di medici e professionisti\u201d, un Progetto di Ricerca che ha l\u2019obiettivo di dare voce alle persone che vivono una situazione di fragilit\ue0 legata ad una patologia cronica ed ai loro famigliari, perch\ue9 possano avere uno spazio in cui condividere l\u2019impatto che la pandemia e il relativo lockdown hanno avuto sulle attivit\ue0 di vita quotidiana, sulla cura della BPCO, sia dal punto di vista pratico sia clinico, ma anche emotivo e sociale

The 5T approach in asthma: Triple Therapy Targeting Treatable Traits

: Using a therapeutic strategy that is free from traditional diagnostic labels and based on the identification of "treatable traits" (TTs), which are influential in clinical presentations in each patient, might overcome the difficulties in identifying and validating asthma phenotypes and endotypes. Growing evidence is documenting the importance of using the triple therapy with ICS, LABA, and LAMAs in a single inhaler (SITT) in cases of asthma not controlled by ICS/LABA and in the prevention of exacerbations. The identification of TTs may overcome the possibility of using SITT without considering the specific needs of the patient. In effect, it allows a treatment strategy that is closer to the precision strategy now widely advocated for the management of patients with asthma. There are different TTs in asthma that may benefit from treatment with SITT, regardless of guideline recommendations. The airflow limitation and small airway dysfunction are key TTs that are present in different phenotypes/endotypes, do not depend on the degree of T2 inflammation, and respond better than other treatments to SITT. We suggest that the 5T (Triple Therapy Targeting Treatable Traits) approach should be applied to the full spectrum of asthma, not just severe asthma, and, consequently, SITT should begin earlier than currently recommended

The Impact of Possible Misuses Conditions on in Vitro Performance of NEXThaler in Comparison with Ellipta Inhaler

: The correct use of dry powder inhalers by the patients is essential to ensure effective treatment and management of the disease. The purpose of the work was to assess the consequence of inhaler misuse in terms of emitted dose and aerodynamic parameters. One reservoir multidose (Foster-NEXThaler®) and one pre-dosed (Relvar-Ellipta®) devices, both sharing the "open, inhale and close" procedure, were the subject of the study. NEXThaler activated at different degrees of slope showed a consistent dose delivery for both the drugs included in the formulation (beclomethasone dipropionate/formoterol fumarate). Contrary, Ellipta showed a decrease of the emitted dose for both fluticasone furoate and vilanterol trifenatate when the device was operated with inclination (-14% at 45° and -22% at 90°). Similarly, the delivered dose of NEXThaler was unaffected by an accidental fall, while Ellipta released FluF and VT doses 50% lower than the control values. The presence of the dose protector in NEXThaler offers the advantage of retaining the powder if the inhaler is subjected to incorrect manipulations. Both products proved to be reliable in double activation. Finally, simulation exhalation conditions had an impact on the aerodynamic profile of the two products

Consequences of not-shaking and shake-fire delays on the emitted dose of some commercial solution and suspension pressurized metered dose inhalers

Pressurized metered-dose inhalers (pMDIs) include hydrofluoroalkane (HFA) propellant to generate a drug aerosol upon actuation and drugs can be formulated as solution or suspension. Suspended particles can cream or sediment depending on density differences between drug and propellant and shaking the pMDI is an essential step to ensure a uniform drug dose release

Successful multimodal treatment of a breast cancer patient with a recurrence invading the chest wall

We describe successful operative management of a solitary breast cancer metastasis in the chest wall after complete response with concomitant non-pegylated liposomal doxorubicin (NPLD) and docetaxel followed by sternal rib resection with prosthetic reconstruction. We report a case of a 41-year-old woman who had a breast cancer recurrence infiltrating neighboring osteo-cartilage of the left sternal body, the cartilaginous portion of the third and fourth ipsilateral ribs and was inseparable from the rear side pectoral reaching deep into contiguity with the pericardium. After 6 cycles of chemotherapy with NPLD plus docetaxel, sternal rib resection with prosthetic reconstruction was performed. Histological examination did not show any evidence of residual tumor. At 9 months of follow-up, the patient appears free of disease. Our case demonstrates that a multimodal approach in patients with chest wall recurrence of breast cancer without distant metastasis, may be safe and effective for maintaining a good quality of life.We describe successful operative management of a solitary breast cancer metastasis in the chest wall after complete response with concomitant non-pegylated liposomal doxorubicin (NPLD) and docetaxel followed by sternal rib resection with prosthetic reconstruction. We report a case of a 41-year-old woman who had a breast cancer recurrence infiltrating neighboring osteo-cartilage of the left sternal body, the cartilaginous portion of the third and fourth ipsilateral ribs and was inseparable from the rear side pectoral reaching deep into contiguity with the pericardium. After 6 cycles of chemotherapy with NPLD plus docetaxel, sternal rib resection with prosthetic reconstruction was performed. Histological examination did not show any evidence of residual tumor. At 9 months of follow-up, the patient appears free of disease. Our case demonstrates that a multimodal approach in patients with chest wall recurrence of breast cancer without distant metastasis, may be safe and effective for maintaining a good quality of life

Sleeve lobectomy versus standard lobectomy for lung cancer. Functional and oncologic evaluation

BACKGROUND: The purpose of this study was to compare functional and oncologic outcome of sleeve lobectomy (SL) with that of standard lobectomy (STL) in patients with non-small cell lung cancer. METHODS: Between January 2009 and April 2013, 44 consecutive patients undergoing upper SL (29 right side, 15 left side) were prospectively enrolled to be compared with 44 patients with the same side distribution who were randomly selected from patients undergoing upper STL during the study period. Functional and oncologic results of the two groups were compared. RESULTS: Pathologic tumor stage ranged between I and IIIa with similar patient distribution between the two groups. Postoperative complication rates were 20.5% in the SL group and 16% in the STL group. There was no postoperative mortality in either group. Mean postoperative decrease in forced expiratory volume in 1 second at 3 months postoperatively was 17.5% ± 6.2% in the SL group and 19% ± 14.8% in the STL group (p = 0.52). There also was no significant difference (p = 0.15) in mean postoperative decrease in 6-minute walk test (64.3 ± 2.5 m versus 69.1 ± 21.4 m) between the two groups. Evaluation of postoperative changes in quality of life at 3 and 6 months based on a standardized questionnaire (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire) did not show significant differences between the SL group and the STL group (p > 0.05) in terms of global health status, physical functioning, and fatigue. Actuarial survival rates at 3 and 5 years, respectively, were 85.3% and 60.1% in the SL group and 88.7% and 58.2% in the STL group, without significant difference (p = 0.68). CONCLUSIONS: Functional and oncologic results of SL are comparable to those of STL in patients with non-small cell lung cancer.BACKGROUND: The purpose of this study was to compare functional and oncologic outcome of sleeve lobectomy (SL) with that of standard lobectomy (STL) in patients with non-small cell lung cancer. METHODS: Between January 2009 and April 2013, 44 consecutive patients undergoing upper SL (29 right side, 15 left side) were prospectively enrolled to be compared with 44 patients with the same side distribution who were randomly selected from patients undergoing upper STL during the study period. Functional and oncologic results of the two groups were compared. RESULTS: Pathologic tumor stage ranged between I and IIIa with similar patient distribution between the two groups. Postoperative complication rates were 20.5% in the SL group and 16% in the STL group. There was no postoperative mortality in either group. Mean postoperative decrease in forced expiratory volume in 1 second at 3 months postoperatively was 17.5% ± 6.2% in the SL group and 19% ± 14.8% in the STL group (p = 0.52). There also was no significant difference (p = 0.15) in mean postoperative decrease in 6-minute walk test (64.3 ± 2.5 m versus 69.1 ± 21.4 m) between the two groups. Evaluation of postoperative changes in quality of life at 3 and 6 months based on a standardized questionnaire (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire) did not show significant differences between the SL group and the STL group (p > 0.05) in terms of global health status, physical functioning, and fatigue. Actuarial survival rates at 3 and 5 years, respectively, were 85.3% and 60.1% in the SL group and 88.7% and 58.2% in the STL group, without significant difference (p = 0.68). CONCLUSIONS: Functional and oncologic results of SL are comparable to those of STL in patients with non-small cell lung cancer