Integrated care pathways for airway diseases (AIRWAYS-ICPs).

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

Elastofibroma dorsi: clinicopathological analysis of 71 cases.

INTRODUCTION: Elastofibroma dorsi (ELD) is a rare soft tissue benign tumor of the chest wall. So far, only a few large series have been reported in the English literature and, to the best of our knowledge, radiological assessment and clinical management remain without consensus. The aim of this study is to provide, on the basis of a single-institutional, homogeneous and large experience, ample evidences to support etiological and "clinical-usefulness-grade" classification hypotheses. MATERIALS AND METHODS: We report observational information on 71 ELD cases and, on the basis of these, we discuss the clinical onset features, radiological and surgical characteristics, as well as pathological and immunohistochemical evidences. RESULTS: In the period between January 1994 and September 2009, 71 consecutive patients (23 male and 48 female; mean age: 60.2 years; standard deviation [SD] ± 8.3 years) with ELD diagnosis were surgically treated at our institution. ELD was right sided in 34 patients (47.9%), left in 25 (35.2%), and bilateral in 12 (16.9%). In nine patients, ELD were diagnosed synchronously and three metachronously. Thirty-eight patients (53.5%) had no significant symptoms; 33 (46.5%) reported a clunking sensation or a localized scapular swelling during the shoulder movements. Sixty-six (93%) patients underwent surgical excision with radical intent while in five patients, a biopsy-only procedure was undertaken. Mean hospital stay was 3.0 days (SD ± 1.2 days) with a morbidity of 10.6% (one case of major postoperative bleeding requested a surgical revision of the hemostasis). At the univariate analysis, the probability of occurrence of morbidity increases with tumor size. All operated patients are alive and well at follow-up with no sign of recurrence and complete resolution of the symptomatology. CONCLUSIONS: ELD is relatively uncommon, benign, and well controlled by radical surgery.

Pneumonectomy with and without induction chemo-radiotherapy for non-small cell lung cancer: short and long-term results from a single centre.

BACKGROUND AND OBJECTIVES:   Pneumonectomy for non small cell lung cancer (NSCLC) after induction radio-chemotherapy (IT) has been associated with high peri-operative risk and its safety and efficacy is still debated. The aim of this retrospective study was to compare short and long-term results of pneumonectomy in patients treated with and without IT (radiotherapy plus chemotherapy) for NSCLC. MATERIALS AND METHODS: From 1995 to 2008, 85 consecutive patients underwent pneumonectomy: 49 received pre-operative radiotherapy and chemotherapy (IT group), and 36 patients did not (non-IT group). Peri-operative and long-term outcomes were compared. RESULTS: Major complications rate was 14.3% for IT group and 16.7% for non-IT group (p = n.s.). Mortality rate was 2% in IT group and 5.5% in non-IT group (p = n.s.). Post-operative hospital stay was significantly longer in the IT group (p < 0.0001) as the need for blood transfusion (p = 0.002). Indeed, the mortality rate was similar in the left- and right-sided operations. 5 years survival was 45.3% for IT group and 38.4% for non-IT group (p = n.s.) and 5 year disease free survival rates were 42.3% vs. 37.8% for the two groups, respectively (p = n.s.). Among the clinical, surgical and pathological features no differences on long term outcomes were found with regards to IT. DISCUSSION: Pneumonectomy is a feasible and safe procedure even after pre-operative IT. Our results showed a prolonged hospitalization and the need for blood transfusion in the IT group.

Pulmonary rehabilitation in lung cancer.

Non-small-cell lung cancer (NSCLC) represents a very severe disease, being its incidence increasingly reported and, nowadays, successfully treatable only when surgery is deemed to be feasible. Furthermore, the disease and the clinical effects related to the complementary therapies (radio and/or chemotherapy) may strongly affect, frequently with dramatic clinical side effects, the patient's ability to endure physical exercise. In such context, the PR(PR), which has already been proved to be useful and effective in other diseases such as COPD, could play a pivotal role. The aim of this review article is, therefore, to analyze the pertinent data recently reported in English literature in order to highlight the role of rehabilitation as complementary therapy in the management of patients with NSCLC. The evidence currently available suggests that, when surgery is indicated, PR is a safe and feasible option, both during pre-operative and post-operative timing.The safety and feasibility of rehabilitation are proven even in inoperable patients, although to date, little evidence has been reported on its role in the overall management of such complex diseases.

Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper.

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.

Multiple primary laryngotracheal adenoid cystic and left thyroid follicular carcinoma with right vocal cord paralysis: the crucial role of surgery.

BACKGROUND: Primary tracheal tumors are rare, accounting for only 0.2% of all thoracic cancers. Adenoid cystic carcinoma (ACC) diagnosed in the trachea is very uncommon and its coexistence with second histologically distinct malignant tumors of he neck region has never been reported. SUMMARY: We now report a case of multiple primary laryngotracheal ACC and thyroid follicular carcinoma surgically successful treated with an incidental 8 years follow-up. CONCLUSIONS: The laringotracheal resection with en-bloc thyroidectomy can be adopted for treating multiple primary tumor of tracheal and thyroid carcinoma with good long-term prognosis.

A case of vomiting in an anorexic achalasic patient.

Wernicke's encephalopathy is a neurological disorder caused by thiamine (vitamin B1) deficiency characterized by vertigo, ataxia, and mental confusion. Wernicke's encephalopathy has a causative association with alcoholism but recently there has been an increased prevalence also in other clinical conditions. In literature potentially fatal Wernicke's encephalopathy onset in an advanced achalasia has been previously reported only once. We describe for the first time an improvement of achalasic symptoms in a young patient affected by end-stage achalasia and anorexia nervosa (coming from ineffective Heller-Dor myotomy) after vitamin B1 supplementation. This case report suggest a potential positive impact of B1 supplementation on end-stage achalasic patients and requires systematic studies to confirm this observation.

Complete transmural gastric migration of PTFE mesh after surgery for a recurrent hiatal hernia.

Complications directly associated with the use of prosthetic materials in large hiatal hernia repair are rarely cited events in the literature. We herein report a case of a 47 year-old woman who came to our attention for a subacute onset of severe dysphagia and weight loss. She previously underwent laparotomic Nissen fundoplication with PTFE dual-mesh cruroplasty for a large recurrent hiatal hernia. With the clinical suspicious of "Tight Nissen", an endoscopy was performed and revealed a circular stenosis in the lower esophagus, a rotation of the stomach and, surprisingly, the presence of PTFE mesh free-moving in the gastric lumen With the use of rattooth forceps, the foreign body was removed and, after few days, the patient underwent a surgical debridement of hiatal scar tissue and a gastropexy procedure. In conclusion, dysphagia may manifest during the early postoperative period after mesh repair antireflux surgery, but such dysphagia usually resolves; if it doesn't or if it worsens, mesh migration must be excluded.

Malignant solitary fibrous tumour of the chest wall: a challenging case.

Solitary fibrous tumors are very rare neoplasms that seldomly appear in extra-serosal soft tissues. In such cases, an accurate preoperative diagnosis is often difficult and challenging, especially in extrapleural ones. Traditionally, extrapleural solitary fibrous tumours have been regarded as indolent neoplasms similar to their intra-thoracic counterparts, although there has been some evidence that this subgroup could be a subset of more aggressive malignant tumours. For these reasons, surgical excision is mandatory and represents, to date, the best therapeutic option. In this article we report a case of a malignant solitary fibrous tumor of the chest wall in a 58-year-old man. Problems related to differential diagnosis and the possible pitfalls that can be encountered in the diagnostic process of such rare tumors are discussed.

Acamprosate modulates experimental autoimmune encephalomyelitis.

OBJECTIVE: This pilot study aimed to determine the efficacy of acamprosate (N-acetyl homotaurine) in reducing the pathological features of experimental autoimmune encephalomyelitis (EAE) which is an animal model for multiple sclerosis (MS). BACKGROUND: The amino acid taurine has multiple biological activities including immunomodulation and neuromodulation. The synthetic acetylated taurine derivative, acamprosate, which crosses the blood-brain barrier more readily compared to taurine, is currently being used for the prevention of alcohol withdrawal symptoms associated with enhanced glutamatergic receptor function and GABA receptor hypofunction. METHODS: EAE was induced in C57BL/6 female mice with myelin oligodendrocyte glyocoprotein, amino acid 35-55. Mice were treated with 20, 100 and 500 mg/kg acamprosate for 21 days. RESULTS: Neurological scores at disease peak were reduced by 21, 64 and 9% in the 20, 100 and 500 mg/kg groups, respectively. Neurological improvement in the 100 mg/kg group correlated with a reduction in numbers of inflammatory lesions and the extent of CNS demyelination. Blood TNF-α levels were significantly reduced in the 500 mg/kg group. DISCUSSION: Acamprosate and other taurine analogs have a potential for future MS therapy.

[Clinical effect of bovine pericardial strips on air leak after stapled pulmonary resection in "frail" patients: early results]. / Impiego clinico di suturatrici rivestite con pericadio bovino nella prevenzione delle perdite aeree postoperatorie in pazienti "fragili" sottoposti a resezione polmonare.

AIM: Postoperative air leaks and in particular persistent air leaks (>5 days) after pulmonary resection still represent a common complication and the first cause of hospital stay delay. Aim of this experimental trial was to investigate the efficacy of the use of bovine pericardium strips (in terms of reduction of postoperative leakage and hospital stay) in "critical" patients (COPD, emphysema etc.) who underwent pulmonary resection. METHODS: From October 2010 to February 2011, eight patients (experimental group, Group A) were preoperative selected and underwent pulmonary resection with bovine pericardium strips (Peri-Strips Dry; Synovis ). The inclusion criteria of a "frail patient" were established by a dedicate pneumologist according with clinical and functional data (predicted postoperative FEV1 ranging from 35% and 80% of the theorical predicted value). For comparison, from January 2010 to September 2010, we retrospectively reviewed the data of 28 patients who satisfied the same inclusion criteria and underwent pulmonary resection with standard surgical procedures. This group of patients represents our control group (Group B). RESULTS: There were no significant differences between the two groups in age, gender, preoperative risk factors for developing a postoperative air leak, preop FEV1 and type of resection. No technical deficiencies in the use of bovine pericardium strips were observed in Group A. Postoperative leakage was significant different in the two groups being persistent air leak detected in 0% in Group A versus 17.8% of Group B (P=0.046). Consequently, chest tube duration (6.75±0.84 days [Group A] vs. 9.70±1.26 days (Group B), P=0.019) and hospital stay (10.13±0.83 days [Group A] vs. 12.95±1.37 days [Group B], P=0.013) were lower in the experimental group. CONCLUSION: Bovine pericardium strips are safe and easy-to-do technique to reduce postoperative air leaks after pulmonary resection in "critical" patients.

Vascular phenotypes in primary non-small cell lung carcinomas and matched brain metastases.

BACKGROUND: Anti-angiogenic therapy with bevacizumab (an anti-vascular endothelial growth factor (VEGF) antibody) predominantly targets immature blood vessels. Bevacizumab has shown a survival benefit in non-small cell lung carcinoma (NSCLC) and has recently been demonstrated to be safe in patients with brain metastases. However, it is not known whether bevacizumab is effective against brain metastases or whether metastases are representative of their primary in terms of VEGF expression, hypoxia, proliferation and vascular phenotype. The aim of this study was to evaluate these factors in a series of matched primary NSCLCs and brain metastases. METHODS AND RESULTS: Immunohistochemistry showed strong correlation of carbonic anhydrase 9 expression (a marker of hypoxia) in primary and secondary cancers (P=0.0002). However, the proliferation index, VEGF expression, microvessel density and the proportion of mature vessels were discordant between primary and secondary cancers. The mean proportion of mature vessels was 63.2% higher in the brain metastases than the primary tumours (P=0.004). Moreover, the vascular pattern of the primary tumour was not representative of the metastasis. CONCLUSIONS: Brain metastases have a significantly higher proportion of mature vasculature, suggesting that they may be refractory to anti-VEGF therapy. These findings may have implications for clinical trials and biomarker studies evaluating anti-angiogenic agents in brain metastases.

Huge primary pericardial liposarcoma.

Liposarcomas are the second most common soft tissue sarcoma in adults. They occur predominantly in the lower limbs and retroperitoneum, whereas primary mediastinal liposarcomas are extremely rare. Liposarcomas are often asymptomatic and may reach a considerable size before causing any symptoms related to direct invasion or compression of other thoracic organs. We report a case of a 69-year-old woman with a giant primary pericardial liposarcoma causing cardiac tamponade and discuss its clinical and imaging features and surgical treatment and review the literature.

The radioguided 111In-pentetreotide surgery in the management of ACTH-secreting bronchial carcinoid.

BACKGROUND AND OBJECTIVES: A correct intra-operative detection of the tumour and, therefore, the complete surgical resection is critical to success in ACTH-secreting bronchial carcinoids. To date, all available preoperative and intra-operative procedures remain not entirely satisfactory. The use of intra-operative 111In-pentetreotide detection could offer a potentially reliable and rapid tool of real time assessment to achieve a radical resection. MATERIALS AND METHODS: In two cases of ACTH-secreting bronchial carcinoids, after a preliminary 111In-pentetreotide scan, radio-guided surgery was performed using a hand-held gamma probe 24 h after i.v. administration of the tracer. RESULTS: The 111n-pentetreotide radioguided surgery with hand-held gamma probe, if compared with pre-operative 111In-pentetreotide, significantly improved the intra-operative surgical management by detecting a millimetric nodule in one case; detecting mediastinal lymph node metastasis in both cases and ruling out any other disease localization. DISCUSSION: Intra-operative 111In-pentetreotide detection appears to be safe and easy to perform. This technique allowed to achieve a complete resection of all the tumor locations, that would have been impossible to detect with conventional surgical approach. On the basis of these results we advocate for a wider investigation of the potentialities connected with the radioguided surgery coupled with pre-operative 111In-pentetreotide scan as a promising procedure in the management of ACTH-secreting bronchial carcinoids.

Multiple roles of nicotine on cell proliferation and inhibition of apoptosis: implications on lung carcinogenesis.

The genotoxic effects of tobacco carcinogens have long been recognized, the contribution of tobacco components to cancerogenesis by cell surface receptor signaling is relatively unexplored. Nicotine, the principal tobacco alkaloid, acts through nicotinic acetylcholine receptor (nAChR). nAChR are functionally present on human lung airway epithelial cells, on lung carcinoma [SCLC and NSCLC] and on mesothelioma and build a part of an autocrine-proliferative network that facilitates the growth of neoplastic cells. Different nAChR subunit gene expression patterns are expressed between NSCLC from smokers and non-smokers. Although there is no evidence that nicotine itself could induce cancer, different studies established that nicotine promotes in vivo the growth of cancer cells and the proliferation of endothelial cells suggesting that nicotine might contribute to the progression of tumors already initiated. These observations led to the hypothesis that nicotine might be playing a direct role in the promotion and progression of human lung cancers. Here, we briefly overview the role and the effects of nicotine on pulmonary cell growth and physiology and its feasible implications in lung carcinogenesis.

Development of novel therapeutic strategies for lung cancer: targeting the cholinergic system.

One of the earliest descriptions of non-neuronal ACh synthesis was by Morris who reported that ACh was synthesized in the placenta [1]; furthermore, Falugi et al. showed the presence of AChE in human fibrosarcoma cells [2]. Afterward, the expression of ACh, AChE, and cholinergic receptors in non-neuronal cells was reported in several studies [3-16]. Indeed, recent data reported that SCLC expresses a cholinergic autocrine loop that can regulate cell growth. Such work demonstrates that SCLC cells have a cholinergic phenotype and that ACh exerts as an autocrine growth factor in human lung tumours [16]. Moreover, it has been recently reported that nicotine in lung adenocarcinoma A549 cells, potently induces Bad phosphorylation at serine (S)112, S136 and S155 in a mechanism involving activation of MAPKs, ERK1/2, PI3K/AKT and PKA through the linking to alpha7-receptors [9]. Bad phosphorylation results in sequestering Bad from mitochondria and subsequently interacting with 14-3-3 in the cytosol [9]. We have recently reported that human malignant pleural mesothelioma expresses a cholinergic system, involved in cell growth regulation. Hence, mesothelioma cells growth is modulated by the cholinergic system in which agonists (i.e. nicotine) have a proliferative effect and antagonists (i.e. curare or alpha-cobratoxin) have an inhibitory effect. Furthermore apoptosis mechanisms are under the control of the cholinergic system (nicotine antiapoptotic via induction of NF-kappaB complexes and phosphorylation of Bad at S112, curare proapoptotic via G0-G1 arrest p21waf-1-dependent, but p53-independent) [16]. The involvement of the non-neuronal cholinergic system in lung cancer and mesothelioma appears reasonable and opens up new translational research strategies.

Chemo-radiotherapy in non-small cell lung cancer: the role of gemcitabine.

Gemcitabine (2'-2'-difluorodeoxycytidine) is a well-known cytotoxic drug and a potent radio-enhancer. We herein report the in vitro evidence of its activity, and the clinical experiences when this drug is administered concurrently with radiation. The phase I-II trials are analyzed, focusing on the recent ability to deliver irradiation with low incidence of side effects.

Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage IIIB non-small cell lung cancer.

BACKGROUND: To evaluate feasibility and safety of induction three-drugs combination chemotherapy and concurrent radio-chemotherapy in stage IIIB NSCLC. PATIENTS AND METHODS: Patients with stage IIIB NSCLC were treated with three courses of induction chemotherapy, cisplatin 50 mg/m(2), paclitaxel 125 mg/m(2) and gemcitabine 1000 mg/m(2) on days 1,8 of every 21 day cycle. Patients without distant progressive disease were then treated with radiotherapy and concurrent weekly gemcitabine (250 mg/m(2)). Toxicity and response of radio-chemotherapy treatment have been assessed. RESULTS: Between Jan 01 and Nov 02, 46 patients were enrolled. Grade 3+ hematological and non-hematological toxicity during the induction phase were 41.3% and 13.1%, respectively. In 38 patients a Clinical Response or Stable Disease was recorded and these patients underwent to concurrent radio-chemotherapy. Grade 3+ hematological and non-hematological toxicities were 8.2% in this group. Further response was observed in 66% of patients. Overall median survival time was 17.8 months, with a 3-year survival rates of 23%. CONCLUSION: Three-drugs induction chemotherapy and concurrent radio-chemotherapy with weekly gemcitabine in locally advanced stage IIIB NSCLC is feasible and safe.