Prognostic grading after complete resection for thymic malignancies.

OBJECTIVE: Despite the World Health Organization (WHO) and Masaoka classifications have been widely accepted as the main describers of prognosis determinants in thymic malignancies, so far, these have been considered independently from one another. We have reviewed our single-centre 40-year results after surgical treatment of thymic malignancies evaluating the inter-relationships between the clinical, surgical and pathological variables and investigating their prognostic impact in completely resected patients. PATIENTS AND METHODS: A surgical series of 347 patients was reviewed and, of these, 305 with complete resection enrolled. Long-term and disease-free survival (LTS, DFS) analyses were performed. Kaplan-Meir curves for WHO histotypes and Masaoka-stages were inspected and matched with the log-rank test; the Cox regression analysis was adopted in a multivariable approach. RESULTS: Considered independently, the WHO-histotypes did not differentiate clearly from one to another in terms of LTS and DFS; however, types A-AB-B1-B2 and B3-C clustered in 2, statistically different, malignancy groups (LTS, DFS: Cox-p < 0.001). Masaoka staging was confirmed to be a relevant prognostic determinant, even if no evident difference between stages I vs II and stages III vs IV emerged when the Masaoka-classification was factored in. Thus, when investigating 13 surgical and pathological factors of invasiveness, these showed a clustering in 2 groups according to the presence/absence of pathological proven infiltration in the peri-thymic structures (LTS, DFS: Cox-p < 0.001). By matching the WHO-malignancy clusters and infiltration clusters, 4 classes may be identified, which proved to have a distinct prognostic significance: (LTS-Cox: stage-I vs stage-II, p = 0.003; III: p < 0.001, IV: p < 0.001; DFS-Cox: stage-I vs stage-II, p < 0.001; III: p < 0.001; IV: p < 0.001). CONCLUSIONS: When analyzing the long-term outcome of patients underwent complete resection for thymic malignancies, the combination between pathological and surgical variables showed accurate prognosis predictability.

A rare case of schwannomatosis incidentally detected by 18F-FDG PET/CT during metabolic evaluation of a chest wall tumor / Un caso poco frecuente de schwannomatosis detectado incidentalmente mediante PET/TC con 18F-FDG durante la evaluación metabólica de un tumor de la pared torácica

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Time-trend analysis of the pulmonary function after surgical treatment for esophageal cancer.

OBJECTIVE: To evaluate, in function of time, the modification of pulmonary function after radical esophagectomy with the aim of identifying clinical and/or surgical predictors of functional worsening. PATIENTS AND METHODS: Data of 57 patients operated from 01/06 to 06/11 were retrospectively reviewed. Thirty-eight patients (67%) underwent transhiatal cervico-laparotomic (CL-Group) and 19 (33%) a Mc-Keown cervico-thoraco-laparotomic esophagectomy (CTL-Group). The pulmonary function has been evaluated before and one month after surgery. The outcome has been benchmarked with demographic/clinical characteristics, the type of operation and the presence of post-operative pulmonary complications (POPCs). RESULTS: Mean age and male/female distribution were 66.6±10.6 yrs and 39/18, respectively. A total of 14 (24% of total sample) POPCs occurred with a significantly higher occurrence in the CTL-Group (71% vs 28%, p < 0.001) and in those patients with a pre-operative concurrent pathological condition (64% in COPD patients vs 36% in patients without COPD, p = 0.021). A global worsening of the spirometric parameters (expressed as the baseline percentage change, Δ) emerged, but this decrease was significantly higher in the CTL-Group in terms of Δ-FVC (p = 0.005) and Δ-FEV1 (p = 0.005). Similarly, those patients who have experienced a POPC, showed a higher reduction of the pulmonary function regardless of the surgical approach when compared with those who did not (Δ-FVC: p = 0.053 and Δ-FEV1%: p = 0.015). CONCLUSIONS: In the context of a global reduction of pulmonary function, patients who underwent trans-thoracic esophagectomy or experienced a POPC showed a significantly worse pattern. These patients could be the "best target" for therapeutic rehabilitative strategies in the pre-operative and/or post-operative setting. This assumption is to be proven through prospective clinical trials.

Cholinergic receptors as target for cancer therapy in a systems medicine perspective.

Epithelial cells not innervated by cholinergic neurons express nicotinic and muscarinic acetylcholine (ACh) receptors (nAChR, mAChR). nAChR and mAChR are components of the auto-/paracrine-regulatory loop of non-neuronal ACh release. The cholinergic control of non-neuronal cells may be mediated by different effects (synergistic, additive, or reciprocal) triggered by these receptors. The ionic events (Ca(+2) influx) are generated by the ACh-opening of nAChR channels, while the metabolic events by ACh-binding to G-proteincoupled mAChR. Effective inter- and intracellular signaling is crucial for valuable cancer cells proliferation and survival. Depending on cancer cell type, different AChR have been identified. The proliferation of airways epithelial cancer cells and pancreatic cancer cells may be under the control of α7-nAChR and M3-mAChR, while breast cancer cells and colon cancer cells are regulated by α9-nAChR, and M3-mAChR, respectively. In turn, these receptors may activate different pathways (Ras-Raf-1-Erk-AKT) as well as other receptors (ß- adrenergicR). nAChR or mAChR antagonists may inhibit cancer growth. Inhibition of M3 by antisense or antagonists (Darifenacin, Tiotropium) reduces lung or colon cancer proliferation, as well as inhibition of α9- nAChR [polyphenol (-)-epigallocatechin-3-gallate] diminishes breast cancer cells growth. α7-nAChR silencing inhibits lung cancer proliferation. Moreover, inhibition of the nAChR-ß-adrenergicR pathway (ß-blockers) could be also useful. This review will describe the future translational perspectives of cholinergic receptors druginhibition in a complex disease such as cancer that poses compelling treatment challenges. Cancer happens as consequence of disease-perturbed molecular networks in relevant organ cells that change during progression. The framework for approaching these challenges is a systems approach.

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).

EUS-guided fine needle tissue acquisition for the diagnosis of pleural metastases from endometrial cancer.

Transesophageal EUS-FNA have become a useful tool in the evaluation of the mediastinum, especially during the staging work-up examination of patients with non-small-cell lung cancer (NSCLC) or other malignancies. We report a challenging case of a 53 years-old woman with an endometrial adenocarcinoma who subsequently presented with right pleural effusion, diffuse pleural thickening with few pleural lesions. The patient referred a long history of exposure to amiantum, this posing a differential diagnosis between primary pleural tumour (mesothelioma) and neoplastic pleural localization of the endometrial cancer. The cytological examination of the pleural effusion (sampled via thoracenthesis) was not adequate to reach a diagnosis. Although a right-video-assisted thoracoscopy was considered the gold standard in this clinical setting to achieve a tissue acquisition of the pleura, an EUS (as the least invasive procedure) was attempted to reach a definitive diagnosis. EUS-FNTA of the pleura was done using a 19-Gauge needle and the pathological and immunophenotypic features were diagnostic for a pleural metastasis of high-grade endometrial serous carcinoma. The patient received adjuvant chemotherapy with a complete regression of the pleural lesions. We take the opportunity of this challenging case to discuss the efficacy and safety of EUS-FNAT to sample the pleural lesions with the use of a large calibre needle if the lesion lies just under the EUS cursor. We may assume that, in selected patients, this technique could be presented as a viable option to the more invasive surgical procedure, which has been previously the gold standard for the pleural tissue acquisition.

Is 18FDG PET/CT evaluation really useful in the diagnosis of elastofibroma dorsi? / ¿Es útil realizar una 18FDG-PET/TAC en la sospecha diagnóstica de elastofibroma dorsi?

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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.

Role of combined 18F-FDG-PET/CT for predicting the WHO malignancy grade of thymic epithelial tumors: a multicenter analysis.

INTRODUCTION: To investigate the performance of combined (18)F-FDG-PET/CT as a predictor of the WHO-classification based malignancy grade in thymic epithelial tumors. METHODS: From 05/06 to 02/12, the data of 47 patients with thymic epithelial tumors assessed by (18)F-FDG-PET/CT before being surgically treated were collected in 3 centers and retrospectively reviewed for the purposes of this study. The SUVmax and the SUVmax/T index (the ratio tumor-SUVmax to tumor-size) have been matched with specific subgroups of the WHO-classification: low-risk thymomas (types A-AB-B1), high-risk thymomas (types B2-B3) and thymic carcinomas (type C). RESULTS: There were 22 men and 25 women (age range: 31-84 yrs). Mean tumor size was 44.7 ± 19.0 mm. The WHO-classification was: type-A #2, type-AB #11, type-B1 #9, type-B2 #9, type-B3 #9 and type-C #7. The SUVmax and the SUVmax/T were found to be predictive factors useful to distinguish thymomas from thymic carcinomas (SUVmax: area under ROC-curve: 0.955, p = 0.0045; SUVmax/T-size: area under ROC-curve: 0.927, p = 0.0022). Moreover, both parameters were found to be correlated with the WHO malignancy grade (low-risk thymomas; high-risk thymomas; thymic carcinoma), Spearman correlation coefficients being 0.56 (p < 0.0001) and 0.76 (p < 0.0001), respectively for the SUVmax and for the SUVmax/T index. In addition, the SUVmax is also significantly correlated with Masaoka stage (Spearman correlation coefficient: 0.30, p = 0.0436) CONCLUSIONS: A significant relationship was observed between (18)F-FDG-PET/CT findings and histologic WHO-classification for this cohort of thymic epithelial tumors. Thus, on the basis of these evidences, we infer that (18)F-FDG-PET/CT may be useful to predict histology and the WHO classes of risk.

Multitarget drugs of plants origin acting on Alzheimer's disease.

The etiopathology of Alzheimer's disease (AD) is extremely complex and heterogeneous, often associated with comorbidities. As a result it may be unlikely that AD may be mitigated by drug acting on a single specific target. The current tendency in drug design and discovery in AD is the rational design or "serendipitous" discovery of new drug entities challenging multiple targets. Since two of the presently approved drugs for AD are based on natural products (galantamine and the physostigmine-derivative rivastigmine), many plants are now under investigation as a potential source of new drugs. Multifunctional drugs often have their origin in natural sources. This review is limited to plant chemicals having different targets with actual (galantamine) or promising (drugs from Crocus sativus, Ginkgo biloba, Salvia species, and Huperzia serrata) clinical evidence in people with dementia or AD.

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.

From traditional European medicine to discovery of new drug candidates for the treatment of dementia and Alzheimer's disease: acetylcholinesterase inhibitors.

The leading Alzheimer's disease (AD) therapeutics to date involves inhibitors of acetylcholinesterase (AChE), which should, in principle, elevate cholinergic signaling and limit inflammation. In spite of the effectiveness in 20%-30% of AD patients, more attention has been paid to find new anti-AChE agents from medicinal plants. Galanthamine, contained in the bulbs and flowers of Galanthus and related genera like Narcissus, represents a good example. The aim of this study is to review the role of possible AChE inhibitors (AChEI) present in plants traditionally used in European medicine for improving memory. Starting from Galanthamine, properties of Melissa species, Salvia officinalis, Arnica chamissonis and Ruta graveolens are discussed to point to the role of these plants as potential sources for the development of therapeutic agents for AD.

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.

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.

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.