In situ labeling of non-accommodating interneurons based on metabolic rates.

Maintaining high frequency firing of narrow action potentials puts a large metabolic load on fast spiking (FS), perisomatic-inhibitory interneurons compared to their slow-spiking, dendrite targeting counterparts. Although the relationship of action potential (AP) firing and metabolism is firmly established, there is no single method to differentiate interneurons in situ based on their firing properties. In this study, we explore a novel strategy to easily identify the metabolically active FS cells among different classes of interneurons. We found that the oxidation of the fluorescent free radical marker 2,7-dichlorodihydrofluorescein (H2DCF) preferentially occurs in interneurons both in slice cultures and acute brain slices. Despite their morphological heterogeneity, almost all DCF-positive (DCF+) neurons belonged to the cluster of non-accommodating FS interneurons. Furthermore, all FS interneurons expressing parvalbumin (PV) both in slice cultures and in acute slices from tdTomato-PVCre transgenic mice were also DCF+. However, only half of the recorded DCF + cells were also PV+, indicating that H2DCF-oxidation occurs in different interneuron classes characterized by non-accomodating AP-firing. Comprehensively enhancing spontaneous neuronal activity led to mitochondrial oxidation of DCF in pyramidal cells as well as interneurons, suggesting that the apparent selectivity towards interneurons represents differences in the underlying metabolic load. While radical-scavenging, inhibition of APs or NO-synthesis, and iron chelation had no effect on the staining pattern, exposure to the complex-I inhibitor, rotenone, prevented interneuronal DCF accumulation. We conclude that H2DCF oxidation is independent of free radicals but correlates with the intensive oxidative energy metabolism and high mitochondrial mass in interneurons sharing the non-accommodating FS phenotype.

Exhaled nitric oxide and carbon monoxide in lung transplanted patients.

BACKGROUND: Exhaled nitric oxide (eNO) and carbon monoxide (eCO) are markers of pulmonary inflammation associated with acute graft rejection and lung infections in lung transplant (LTX) recipients. Regarding eNO and eCO levels in LTX patients affected by bronchiolitis obliterans syndrome (BOS), published data are discordant. OBJECTIVES: We aim to evaluate eNO at multiple flows, alveolar concentration of nitric oxide (CalvNO), maximum conducting airway wall flux (J'awNO) and eCO levels in LTX patients to assess the potential role of these parameters in BOS evaluation. METHODS: Fractional exhaled nitric oxide (FeNO), CalvNO and J'awNO were analysed in 30 healthy subjects and 27 stable LTX patients (12 BOS patients). Pulmonary function tests were performed after eNO and eCO assessment. Receiver operating characteristic (ROC) curves were conducted to evaluate diagnostic accuracy for BOS of eNO parameters. RESULTS: LTX patients reported higher values of FeNO at flow rates of 50 (p < 0.01), 150 (p < 0.05), 350 ml/s (p < 0.001), and CalvNO (p < 0.0001) than healthy controls. BOS patients showed higher FeNO at flow rates of 150 (p < 0.05) and 350 ml/s (p < 0.01) and CalvNO (p < 0.001) than non-BOS patients. CalvNO reported a remarkable diagnostic accuracy for BOS (AUC: 0.82). There were no significant differences of eCO levels between LTX patients and healthy controls. CONCLUSION: LTX patients affected by BOS showed higher levels of FeNO 150 and 350, and CalvNO than non-BOS LTX patients, probably due to chronic airway inflammation and fibrotic remodelling. CalvNO may be a potential biomarker of BOS in LTX patients.

Lung resection for non-small cell lung cancer after prophylactic coronary angioplasty and stenting: short- and long-term results.

AIM: Recent studies have reported a high incidence of perioperative in-stent trombosis with myocardial infarction (MI), in patients undergoing non-cardiac surgery, early after coronary angioplasty and stenting. The short and long-term results of surgery for non-small cell lung cancer (NSCLC) after prophylatic coronary angioplasty and stenting were analyzed. METHODS: Prospective collected data were examined for postoperative complications and long-term survival in 16 consecutive patients who underwent mayor lung resection for NSCLC after prophylactic coronary angioplasty and stenting for significant coronary artery disease , from 2001 to 2008. One and two non-drug-eluting stents were placed in 75% or (25% of the patient, respectively. All patients had four weeks of dual antiplatelet therapy, that was discontinued 5 days prior to surgery and replaced by low molecular weight heparin. Patients were keep sedated and intubated overnight, according to our protocol. RESULTS: There were no postoperative deaths nor MI. A patient experienced pulmonary embolism with moderate troponin release and underwent coronary angiography that showed patency of the stent. Two patients developed postoperative bleeding complications haemothorax requiring a re-thoracotomy in 1, gastric bleeding requiring blood transfusion in 1. At the mean follow-up of 30 months (range 3-95), none of the patients showed evidence of myocardial ischemia, while 5 (31%) patients died, mostly (N.=4) due to distant metastasis. The five-year survival rate was 53%. CONCLUSION: In contrast to previous reports, lung resection after prophylactic coronary angioplasty and stenting is a safe and effective treatment for NSCLC and myocardial ischemia. The application of a refined protocol could be the key factor for improved results.

Pleural granuloma mimicking malignancy 42 years after slurry talc injection for primary spontaneous pneumothorax.

BACKGROUND: Talc poudrage is considered a safe pleurodesis technique to improve the results of video-assisted thoracoscopic surgery in cases of primary spontaneous pneumothorax (PSP). METHODS: We report the case of a patient with left pleural pseudo-nodular plaque and a high metabolic rate upon PET scan suspected for malignancy, occurring 42 years after slurry talc injection for conservative treatment of PSP. The patient presented with coughing, chest pain and weight loss. Thoracotomy was required to obtain a diagnosis and perform a complete pleurectomy. RESULTS: Histology was conclusive for pleural talc granuloma. CONCLUSIONS: Indications and possible complications of talc use in young patients with PSP, and the management of possible consequent pleural lesions suspected for malignancy, need to be investigated.

VATS for congenital lobar emphysema: a case report.

UNLABELLED: Congenital lobar emphysema (CLE) is a rare congenital lung disease consisting in overinflation of a pulmonary lobe. Adult onset of CLE is therefore unusual, often presented with mild symptoms. The authors report a very uncommon case of congenital segmental emphysema diagnosed in a 21-year-old non-smoking man because of recurrent right pneumothorax. Indication to pulmonary resection was established according to functional limitation, radiological findings of right upper lobe segmental emphysema with corresponding bronchial agenesia, scintigraphic result of extremely reduced ventilation and perfusion of lung emphysematous area and recurrency of pneumothorax. The intervention was carried out by 3-portal video-assisted thoracic surgery (VATS) using single-lung ventilation leading to determine precisely how much lung to resect thanks to the obvious and clear-cut distinction between functioning and non functioning parenchyma of the upper lobe. A stapler wedge resection by VATS was thus obtained, that, as far as the author's knowledge, it is the first case of endoscopic parenchymal sparing resection in CLE. Even though congenital lobar emphysema is rare, clinical awareness of this condition is important for early diagnosis and effective surgical treatment that in this case led to favourable RESULTS: The VATS procedure seems to be an advantageous approach.

Transmanubrial osteomuscolar sparing approach for T1-T2 thoracic disc herniation.

Herniated thoracic disks are rare entities and their surgical treatment comprises 0.15% to 4% of all disk operations. Surgical approaches have included pediculectomy, costotransversectomy, lateral extracavitary, transthoracic thoracotomy, and thoracoscopy. The authors present a transmanubrial osteomuscular sparing approach for the treatment of T1-T2 thoracic disc herniation that is likely to be the only one described in the literature for this disease so far.

Myelodysplasia and Good syndrome. A case report.

Good syndrome (GS) is a rare adult-onset immunodeficiency disease characterised by hypogammaglobulinaemia and thymoma. Here we describe a 72-year-old male patient who was diagnosed with GS when he was 62, after a two-year history of recurrent respiratory infections. A chest CT scan showed a mediastinal mass which was surgically removed; its histology revealed a thymoma. The patient was hypogammaglobulinaemic and his clinical condition dramatically improved after starting an appropriate dosage of IVIG. Two years ago he developed a normochromic normocytic anaemia requiring several transfusions. A bone marrow biopsy revealed a myelodysplastic syndrome. The patient started cyclosporine and the anaemia gradually improved, achieving transfusion independence.

Pattern of recurrence and survival of c-Ia NSCLC diagnosed by transpleural methods.

AIM: The aim of this study was to evaluate if transpleural diagnostic methods as percutaneous fine-needle aspiration biopsy (FNAB) or tumour wedge resection by video-assisted thoracoscopic surgery (VATS) impact on local recurrence and long term survival of patients affected by non-small cell lung cancer (NSCLC). METHODS: Records concerning 179 patients with peripheral c-Ia NSCLC who underwent complete resection from 1994 to 2000 have been reviewed. Patients were randomized into two groups according to the diagnostic method employed, as follows: in group I (N.=63) diagnosis was obtained by bronchoscopy; in group II (N.=116) diagnosis was obtained by FNAB (N.=59) or tumour wedge resection by VATS (N.=57) after a negative bronchoscopy. Survival curves were compared using log-rank test. Distribution of frequencies was analyzed with Chi-square and Fisher's exact test. RESULTS: The two groups of patients did not significantly differ in terms of age, gender, forced expiratory volume in 1 second, comorbidities, histological type and tumour size; pathologic stage IIb was more frequent in group I. At a median follow-up of 48 months, (range 2-108 months), local recurrence was found in 9.5% (N.=6) of the patients in group I and in 12.5% (N.=15) of patients in group II (P=NS); distant metastasis were found in 28.6% (N.=18) of patients in group I and in 13.8% (N.=16) in group II (P=0.03). Patients in group II had a statistically better five-year survival rate than patients in group I (70% and 55% respectively P=0.016). CONCLUSION: FNAB and tumour wedge resection by VATS represent valuable diagnostic methods for lung cancers, since they do not seem to increase the risk of local recurrence. On the other hand, tumours diagnosed by bronchoscopy have a worse prognosis, that may be related to their higher metastatic potential rather than to diagnostic procedure itself.

Chemo-hormone therapy of non-well-differentiated endocrine tumours from different anatomic sites with cisplatinum, etoposide and slow release lanreotide formulation.

We report the results of a phase II trial in patients with metastatic endocrine tumours from different sites, which aimed to evaluate the anti-tumour activity and toxicity of a cisplatinum and etoposide regimen administered in combination with the somatostatin agonist lanreotide given in slow release formulation. Between January 1999 and November 2003, 27 patients with histological diagnoses of endocrine tumours with different degrees of differentiation, excluding well differentiated carcinoid neoplasms, received intravenous (i.v.) administration of cisplatinum (30 mg m(-2)) and etoposide (100 mg m(-2)) on days 1-3 and intramuscular administration of 60 mg lanreotide on day 1, in a 21-day cycle. All of the patients were evaluable for toxicity and response. The treatment was very well tolerated as no grade 4 toxicity was observed. Four patients achieved a complete response, six a partial response, 12 experienced disease stabilisation and five disease progression. The average time to progression and to survival were 9 and 24 months respectively. These results suggest that this chemo-hormone therapy regimen is well tolerated and active in patients with non-well differentiated endocrine tumours.

A rare case of malignant diaphragmatic hemangiopericytoma in a patient with pleural effusion.

This paper reports a case of primary malignant diaphragmatic hemangiopericytoma in a 30-year-old male patient operated on for a diaphragmatic mass. The tumour was discovered on a TC scanning performed to explain the etiology of an exudative pleural effusion in a patient admitted for dyspnea, fever and thoracic pain. Given the rarity of this disease, the histological and pathological features of hemangiopericytoma are discussed in the light of the new classification system for soft tissue and bone tumours, as well as its currently accepted therapeutical guidelines.

A novel metronomic chemotherapy regimen of weekly platinum and daily oral etoposide in high-risk non-small cell lung cancer patients.

The aim of this pilot phase II trial was to investigate the toxicity and anti-tumour activity of a novel metronomic regimen of weekly cisplatin (CDDP) and oral etoposide (VP16) in high-risk patients with advanced NSCLC. The study enrolled 31 high-risk patients (27 men and 4 women aged 16-82 years; mean, 64.3) with NSCLC (18 stage IIIB and 13 stage IV) and an ECOG performance status of < or = 3, all of whom received weekly CDDP 30 mg/m2 iv on days 1, 8, 14 and 28 of each cycle and oral daily etoposide 50 mg/m2 on 21 of the 28 days. The most frequent adverse events were grade III leukopenia and anemia; nevertheless, three patients died of pulmonary embolism after 2, 3 and 6 weeks of treatment. The objective response (OR) rate was 45.2% (2 complete and 12 partial), and the disease control rate was 58.1% (14 ORs and 4 disease stabilisations). The mean time to progression and survival were respectively nine months (95% CI, 6.3-15.8 months) and thirteen months (95% CI, 9.1-20.5 months). Pharmacological analysis showed that this metronomic regimen allows a much greater median monthly area under the curve of CDDP and VP16 than conventional treatment schedules. Our findings also suggest that this treatment schedule may affect tumour growth and neoangiogenesis by changing peripheral blood vascular-endothelial growth factor levels. These preliminary results indicate that our metronomic regimen is well tolerated and active, even in patients with a very poor prognosis.

[University training for coordinators]. / La formazione universitaria dei Coordinatori.

We need an adequate quality level of information between the building design and manufacturing process for Health and Safety in the work site. A fully-developed communication system is needed, for H&S Coordinators, in order to integrate alphanumerical and graphical protocols. The Aim is: (1) to organise information on the building process, keeping communications in function of everyone's needs; (2) to carry out an audit process ensuring that all levels of contractors personnel are implementing the Project of Health and Safety Management Plan effectively; (3) To make all that with a Program Interface relatively simple. The synergy between Safety Manager and Designers generates a system output integrating all sorts of alphanumerical, graphical information and prescriptions. This system output has several targets: (1) to integrate Design and H&S in a specific Data-Base; (2) to define the preconditions of the work phases; (3) to develop the Work Program of Enterprise in function of the Health and Safety Plan in compliance with the contractor site-specific plan; (4) to develop a program process for the audit; (5) to review the contractor's Project for H & S; (6) to manage responsibility; (7) to keep corrective action.

A case of primary malignant hemangiopericytoma of the heart with fatal outcome.

Hemangiopericytoma is a rare, highly vascular tumor which has both malignant and benign varieties. We report a case of a 41-year-old man who underwent surgery in emergency because of cardiac tamponade. The histopathologic examination of the specimens revealed primary malignant cardiac hemangiopericytoma. The patient died 46 days from the beginning of symptoms and 13 days after surgery.

Late outcome and perioperative complications for surgery of locally recurrent bronchogenic carcinoma.

AIM: Many doubts involve a 2(nd) surgical approach for local relapse of non small cell lung cancer (NSCLC) since iterative resections represent a well-recognized treatment in second primary lung cancer (SPLC). METHODS: The medical reports of patients who underwent surgical resection, between 1988 and 2002, were reviewed. All patients submitted to 2(nd) operation were examined according to Martini and Melamed criteria to distinguish between local recurrence and second primary lung cancer. RESULTS: Complete resection for NSCLC was performed in 1 386 patients. Nineteen patients were submitted to surgery for local recurrence (17 men and 2 women) and mean age at the time of 1(st) operation was 61 years (range 41-78 years). The 1(st) operation consisted of lobectomy in 15 cases, anatomical segmentectomy in 2 and wedge resection in 2. The 2(nd) pulmonary resection was completion pneumonectomy in 16 cases, completion lobectomy in 2, wedge resection in 1. Major complications occurred in 26% and overall hospital mortality was 5%. Five-year survival after 2(nd) intervention was 31% and median survival 27 months. Survival was better when the time between 1(st) resection and cancer relapse was longer than 14 months and when recurrence was intrapulmonary. CONCLUSIONS: A new malignant lesion can be operated if it is solitary and intrapulmonary, if accurate staging is negative and if the patient is able to go through 2(nd) surgery from cardiopulmonary evaluation.

Ten year experience of bioabsorbable mesh support in pectus excavatum repair.

INTRODUCTION: We reviewed 10 years experience in the treatment of this deformity using a retro-sternal bioabsorbable mesh in place of a metallic device to lift and stabilise the sternum. Moreover, the mesh supports the thoracic and upper abdominal wall reconstruction. MATERIALS AND METHODS: From January 1990 to December 2000, in our Thoracic Surgery Unit, 65 patients with PE were assessed for surgical repair, mean age 16+/- 3.5 years, fronto sagittal thoracic index (FSTI) 0.21, ranging from 0.15-0.33. Twenty-three of them underwent surgical correction after initial assessment, 22 were deferred and sent to physiotherapy. At a subsequent assessment, five of the patients sent to physiotherapy were deemed to require surgery. RESULTS: Of the 28 patients who underwent surgery, 2 (10%) presented a mild recurrence of PE after 1 year (0.300.34), meanwhile all other patients maintained a FSTI>0.34. For all patients the improvement in FSTI was statistically significant, p = 0.001. Patients satisfaction after 24 months was thus shared: excellent 18 patients (65%), good seven patients (25%), fair one patient (3.5%) and poor two patients (7%). No major complications were observed in preoperative period. Patients mobilisation was soon achieved thanks to the postoperative pain control and the absence of retro-sternal metallic support. CONCLUSIONS: The introduction of bioabsorbable mesh in the Robicsek technique is a safe procedure related to a high percentage of success. The high tolerance of the material reduces the inflammatory reaction. Moreover, the procedure prevents patients from having complications caused by retro-sternal device dislodgment, avoiding a second intervention for device reposition and reducing the postoperative chest pain achieving an early patient mobilisation. In the end a complete reconstruction of the upper abdomen wall has been produced.

Right pneumonectomy for adenocarcinoma stage IIIA-N2 in a heart transplant patient after induction chemotherapy.

Lung tumors are the most frequent solid tumor in the heart transplant population. Unfortunately, most of these patients are in an advanced stage of disease at the time of presentation, which carries a poor prognosis. We present a heart transplant patient with histologically proven. Stage IIIA-N2 bronchogenic adenocarcinoma who had complete lymph-node downstaging after induction chemotherapy and underwent a complete tumor resection by right pneumonectomy.

Comparison between segmentectomy and larger resection of stage IA non-small cell lung carcinoma.

AIM: Stage IA non small cell lung carcinoma (NSCLC) represents early cancer and is best treated by surgery. The frequency of recurrence and new primary cancer varies from one report to another while the role of sublobar resection is still debated. METHODS: We retrospectively reviewed 121 consecutive patients with pathological stage IA after radical surgery. RESULTS: In stage IA NSCLC 1-, 3-, 5-year survival rates were 89%, 76% and 66%. Nearly half of the deaths were unrelated to the original cancer. From statistical analysis we did not find any factor indicative of a better prognosis. We did not find any difference in survival between histologic types. Segmentectomy did not show a worse survival rate compared with larger resection. CONCLUSION: Survival is neither influenced by the type of resection nor by the histologic types in stage IA. However, we noticed a high incidence of local recurrence, segmentectomy could be a viable choice in patients with cardiopulmonary impairment.

Sudden onset of thoracic pain: neurofibroma with intracystic haemorrhage.

Intercostal nerve sheath tumors are normally benign and asymptomatic. Nevertheless surgical resection can eliminate the risk of malignant transformation and also achieve complete remission in case of symptoms.