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1.  Experimental evaluation of a new system for laser tissue welding applied on damaged lungs† 
OBJECTIVES
Alveolar air leaks represent a challenging problem in thoracic surgery, leading to increased patient morbidity and prolonged hospitalization. Several methods have been used, but no ideal technique exists yet. We investigated the lung-sealing capacity of an experimental kit for laser tissue welding.
METHODS
The kit is composed of a semiconductor laser system applied on a protein substrate associated with a chromophore that increases absorption. In vitro tests on porcine lung tissue were done to define ideal laser parameters (power 100 Å, frequency 50 Hz, pulse duration 400 µs) and protein substrate dilution (50%). For in vivo tests, through a left thoracotomy, 14 pigs received two different lung damages: a linear incision and a circular incision. Protein substrate applied on damaged areas was treated with laser to obtain a layer that reconstituted the integrity of the visceral pleura. Air leaks were intraoperatively evaluated by water submersion test with an airway pressure of 20 cmH2O. Animals were sacrificed at postoperative days 0 and 7 to study early and late pathological features.
RESULTS
After applying laser treatment, no air leaks were seen in all proofs except in 2 cases in which a second application was required. At time 0, pathological damage mostly consisted of superficial alveolar necrotic tissue covered by protein membrane. At time 7, a complete recovery of lung lesions by fibrous scar with slight inflammatory reaction of adjacent lung tissue was seen.
CONCLUSIONS
This experimental study demonstrated the effectiveness of laser tissue welding applied to seal air leaks after lung surgery. Further studies are needed to verify acceptability for human application.
doi:10.1093/icvts/ivt029
PMCID: PMC3630433  PMID: 23396621
Laser tissue welding; Air leak; Lung; Aerostasis
2.  Thymectomy for thymoma and myasthenia gravis. A survey of current surgical practice in thymic disease amongst EACTS members† 
Thymic disorders, both oncological and non-oncological, are rare. Multi-institutional, randomized studies are currently not available. The Thymic Working Group of the European Association for Cardio-Thoracic Surgery (EACTS) decided to perform a survey aiming to estimate the extent and type of current surgical practice in thymic diseases. A questionnaire was addressed to the thoracic and cardio-thoracic members of the society, and the answers received from 114 participants were analysed. High-volume surgeons cooperate more frequently with a dedicated neurologist and anaesthesist (P = 0.04), determine more frequently neurological scores pre- and postoperatively (P = 0.02) and do not operate on thymic hyperplasia in stage I myasthenia gravis (MG) (P = 0.04). High-volume thymoma surgeons more often use a transpleural approach for stage I thymoma < 4 cm (P = 0.01), induction therapy (P = 0.05) and are more likely to have access to a tissue bank (P = 0.04). Both in thymoma and MG surgery, cooperative prospective studies seem to be feasible in dedicated thoracic surgical associations as EACTS.
doi:10.1093/icvts/ivs046
PMCID: PMC3352719  PMID: 22374292
Thymoma; Myasthenia gravis; Thymectomy; Survey
3.  Herpes Virus Infection Is Associated with Vascular Remodeling and Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis 
PLoS ONE  2013;8(2):e55715.
Background
Pulmonary hypertension (PH) represents an important complication of idiopathic pulmonary fibrosis (IPF) with a negative impact on patient survival. Herpes viruses are thought to play an etiological role in the development and/or progression of IPF. The influence of viruses on PH associated with IPF is unknown. We aimed to investigate the influence of viruses in IPF patients focusing on aspects related to PH. A laboratory mouse model of gamma-herpesvirus (MHV-68) induced pulmonary fibrosis was also assessed.
Methods
Lung tissue samples from 55 IPF patients and 41 controls were studied by molecular analysis to detect various viral genomes. Viral molecular data obtained were correlated with mean pulmonary arterial pressure (mPAP) and arterial remodelling. Different clinical and morphological variables were studied by univariate and multivariate analyses at time of transplant and in the early post-transplant period. The same lung tissue analyses were performed in MHV-68 infected mice.
Results
A higher frequency of virus positive cases was found in IPF patients than in controls (p = 0.0003) and only herpes virus genomes were detected. Viral cases showed higher mPAP (p = 0.01), poorer performance in the six minute walking test (6MWT; p = 0.002) and higher frequency of primary graft (PGD) dysfunction after lung transplant (p = 0.02). Increased arterial thickening, particularly of the intimal layer (p = 0.002 and p = 0.004) and higher TGF-β expression (p = 0.002) were demonstrated in viral cases. The remodelled vessels showed increased vessel cell proliferation (Ki-67 positive cells) in the proximity to metaplastic epithelial cells and macrophages. Viral infection was associated with higher mPAP (p = 0.03), poorer performance in the 6MWT (p = 0.008) and PGD (p = 0.02) after adjusting for other covariates/intermediate factors. In MHV-68 infected mice, morphological features were similar to those of patients.
Conclusion
Herpesviral infections may contribute to the development of PH in IPF patients.
doi:10.1371/journal.pone.0055715
PMCID: PMC3585298  PMID: 23468849
4.  A pathological complete response after preoperative chemotherapy with carboplatin and pemetrexed in malignant pleural mesothelioma: A case report. 
Malignant pleural mesothelioma is an aggressive tumour with poor prognosis and short duration of response probably due to the high chemo-refractoriness. Multimodality treatment based on preoperative chemotherapy, surgery and adjuvant radiotherapy seems to be a feasible and effective therapeutic option in selected patients.We report on a case of pathological complete response in a patient affected by malignant pleural mesothelioma who was treated with four cycles of preoperative chemotherapy based on carboplatin plus pemetrexed followed by parietal pleurectomy and lung decortication. Carboplatin plus pemetrexed was a well tolerated regimen without grade 3-4 haematological toxicity, and this confirm the feasibility of such a treatment as an alternative to the current golden standard based on cisplatin plus pemetrexed.Complete resection allows the pathologist to better describe biological markers of mesothelioma cells, in order to select patients with different treatment outcome and prognosis.
doi:10.3978/j.issn.2072-1439.2010.02.04.2
PMCID: PMC3256467  PMID: 22263055
mesothelioma; chemotherapy; carboplatin; pemetrexed
5.  Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema 
Respiratory Research  2005;6(1):14.
Background
Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema.
Methods
In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 α1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations. Six unused donor lungs served as controls. Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1). The role of the transforming growth factor (TGF)-β1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate.
Results
The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p ≤ 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p ≤ 0.01 vs p = 0.09). The proliferation index was similar in patients and controls (1.9 ± 2.2 vs 1.7 ± 1.1). An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p ≤ 0.05). TGF-β1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p ≤ 0.05). A positive correlation between TGF-βRII and AI was observed only in the control group (p ≤ 0.005, r2 = 0.8). A negative correlation was found between the TGF-β pathway (particularly TGF-βRII) and T lymphocytes infiltrate in smoking-related cases (p ≤ 0.05, r2 = 0.99)
Conclusion
Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease. The TGFβ-1 pathway does not seem to directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-β1 may differently orchestrate cell fate in AAT and smoking-related emphysema types.
doi:10.1186/1465-9921-6-14
PMCID: PMC549521  PMID: 15705190
apoptosis; proliferation; end-stage emphysema

Results 1-5 (5)