Giuseppe Marulli

Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema.

BackgroundApoptosis has recently been proposed to contribute to the pathogenesis of emphysema.MethodsIn 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.ResultsThe 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)ConclusionOur 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.

Robot-aided thoracoscopic thymectomy for early-stage thymoma: A multicenter European study

OBJECTIVE Minimally invasive thymectomy for stage I to stage II thymoma has been suggested in recent years and considered technically feasible. However, because of the lack of data on long-term results, controversies still exist on surgical access indication. We sought to evaluate the results after robot-assisted thoracoscopic thymectomy in early-stage thymoma. METHODS Data were collected from 4 European centers. Between 2002 and 2011, 79 patients (38 men and 41 women; median age, 57 years) with early-stage thymoma were operated by left-sided (82.4%), right-sided (12.6%), or bilateral (5%) robotic thoracoscopic approach. Forty-five patients (57%) had associated myasthenia gravis. RESULTS Average operative time was 155 minutes (range, 70-320 minutes). One patient needed open conversion, in 1 patient a standard thoracoscopy was performed after robotic system breakdown, and in 5 patients an additional access was required. No vascular and nervous injuries were recorded, and no perioperative mortality occurred. Ten patients (12.7%) had postoperative complications. Median hospital stay was 3 days (range, 2-15 days). Median diameter of tumor resected was 3 cm (range, 1-12 cm), and Masaoka stage was stage I in 30 patients (38%) and stage II in 49 patients (62%). At a median follow-up of 40 months, 74 patients were alive and 5 had died (4 patients from nonthymoma-related causes and 1 from a diffuse intrathoracic recurrence), with a 5-year survival rate of 90%. CONCLUSIONS Our data indicate that robot-enhanced thoracoscopic thymectomy for early-stage thymoma is a technically sound and safe procedure with a low complication rate and a short hospital stay. Oncologic outcome seems good, but a longer follow-up is needed to consider this as a standard approach definitively.

Surgical and neurologic outcomes after robotic thymectomy in 100 consecutive patients with myasthenia gravis.

OBJECTIVE Thymectomy is a well-defined therapeutic option for patients with myasthenia gravis; however, controversies still exist about the surgical approach, indication, and timing for surgery. We reviewed our experience reporting surgical and neurologic results after robotic thymectomy in patients with myasthenia gravis. METHODS Between 2002 and 2010, 100 patients (74 female and 26 male; median age, 37 years) underwent left-sided robotic thymectomy using the da Vinci robotic system (Intuitive Surgical, Inc, Sunnyvale, Calif). The Myasthenia Gravis Foundation of America classification was adopted for pre- and postoperative evaluation. Preoperative Myasthenia Gravis Foundation of America class was I in 10% of patients, II in 35% of patients, III in 39% of patients, and IV in 16% of patients. RESULTS Median operative time was 120 (60-300) minutes. No death or intraoperative complications occurred. Postoperative complications were observed in 6 patients (6%) (bleeding requiring blood transfusions in 3, chylothorax in 1, fever in 1, and myasthenic crisis in 1). Median hospital stay was 3 days (range, 2-14 days). Histologic analysis revealed 76 patients (76%) with hyperplasia, 7 patients (7%) with atrophy, 8 patients (8%) with small thymomas, and 9 patients (9%) with normal thymus; ectopic thymic tissue was found in 26 patients (26%). Clinical follow-up showed a 5-year probability of complete stable remission and overall improvement of 28.5% and 87.5%. Remission was significantly associated with preoperative I to II Myasthenia Gravis Foundation of America class (P = .02). A significant improvement rate was found in Myasthenia Gravis Foundation of America class I to II (P = .03) and AbAchR+ (P = .04). A high percentage of patients interrupted or reduced their medications. CONCLUSIONS Robotic thymectomy is a safe and effective procedure. We observed a neurologic benefit in a great number of patients. A better clinical outcome was obtained in patients with early Myasthenia Gravis Foundation of America class.

Allograft sternochondral replacement after resection of large sternal chondrosarcoma

Surgical excision with a safety margin is the cornerstone of treatment of malignant sternal tumors. After sternal resection, the primary goals of chest wall reconstruction are to prevent flail chest with ventilatory impairment, protect the underlying mediastinal structures, and avoid chest deformity. Various techniques and several materials have been used over the years for this purpose. This report describes the use of sternal allograft to reconstruct the chest wall after sternal resection.

A quarter of a century experience with sleeve lobectomy for non-small cell lung cancer.

OBJECTIVE Sleeve lobectomy represents an effective and widely accepted surgical therapy for non-small cell lung carcinoma (NSCLC). We sought to review our experience in terms of mortality, early and late morbidity, and long-term survival evaluating the technical progresses overtime. MATERIAL AND METHODS From 1980 to 2005, 199 patients underwent sleeve lobectomy. Pathology revealed 167 (83.9%) squamous carcinomas, 23 (11.6%) adenocarcinomas, 7 (3.5%) large cell and 2 (1%) adenosquamous carcinomas. In 39 (19.6%) patients a vascular procedure was associated. Nineteen (9.5%) patients had preoperative radiotherapy, 14 (7%) preoperative chemotherapy and 10 (5%) chemoradiotherapy. RESULTS Overall postoperative mortality was 4.5% (n=9) and morbidity was 17.9% (n=34). Preoperative radiotherapy was identified as a significant risk factor for perioperative mortality (OR: 5.34, 95% CI: 1.16-24.47; p=0.03) and early anastomotic complications (OR: 3.73, 95% CI: 1.01-13.68; p=0.04). Overall 5-year survival rate was 39.7% and stage-by-stage analysis did not reach a significant survival difference. With growing skills the number of procedures, associated angioplasty and difficult sleeves (such as sleeve bilobectomy) increased. Also in term of mortality, in the last 10 years we had 0.8% of mortality rate. CONCLUSIONS Sleeve lobectomy is a safe and effective therapy for selected patients with NSCLC. Vascular procedures and the use of induction chemotherapy did not increase mortality and morbidity; otherwise, the use of preoperative radiotherapy is not recommended. Overtime trend showed a significant lower mortality in the last period. This emphasises the importance of a learning curve and encourages the performance of this procedure in experienced centres.

Single-staged laryngotracheal resection and reconstruction for benign strictures in adults

Laryngotracheal stenosis (LTS) is a challenging problem, and its management is complex. This study evaluated both short- and long-term outcomes following laryngotracheal resection and anastomosis. Between 1994 and 2006, 37 patients underwent surgery for LTS. The cause of stenosis was post-intubation or post-tracheostomy injury in 28 cases and idiopathic in nine. Pearsons technique was used for anterolateral cricotracheal resection (n=23), and Grillos technique of providing a posterior membranous tracheal flap was used in cases of circumferential stenosis (n=14). Since 1998, we have modified the techniques in 21 cases, using a continuous 4/0 polydioxanone suture for the posterior part of the anastomosis. No peri-operative mortality was recorded. Three (8.1%) patients developed major complications (two fistulae and one early stenosis) that required a second surgical look. We had 16 minor complications in 14 (37.8%) patients. The long-term results were excellent to satisfactory in 36 patients (97.3%) and unsatisfactory in one (2.7%). Single-staged laryngotracheal resection is a demanding operation, but can be performed successfully with acceptable morbidity in specialized centers. The continuous suture in the posterior part of the anastomosis simplifies the procedure without causing technique-related complications. In our experience, this procedure guaranteed excellent to satisfactory results in more than 90% of patients.

Titanium plates support for chest wall reconstruction with Gore-Tex dual mesh after sternochondral resection.

We present a case of chest wall reconstruction after sternochondral resection for sternal metastasis of breast origin. We used three transverse titanium plates to stabilise the chest wall and provide support for a polytetrafluoroethylene dual mesh, which was used to cover the chest wall defect. The pectoralis muscles flaps were approximated in the midline to cover the dual mesh.

Overexpression of squamous cell carcinoma antigen in idiopathic pulmonary fibrosis: clinicopathological correlations

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disorder with a poor prognosis. Epithelial instability is a crucial step in the development and progression of the disease, including neoplastic transformation. Few tissue markers for epithelial instability have been reported in IPF. Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor typically expressed by dysplastic and neoplastic cells of epithelial origin, more often in squamous cell tumours. At present, no information is available on its expression in IPF. Methods: SCCA and transforming growth factor β (TGFβ) expression in surgical lung biopsies from 22 patients with IPF and 20 control cases was examined. An in vitro study using A549 pneumocytes was also conducted to investigate the relationship between SCCA and TGFβ expression. SCCA and TGFβ epithelial expression was evaluated by immunohistochemistry and reverse transcription–PCR (RT-PCR). SCCA values were correlated with different pathological and clinical parameters. Time course analysis of TGFβ expression in A549 pneumocytes incubated with different SCCA concentrations was assessed by real time RT–PCR. Results: SCCA was expressed in many metaplastic alveolar epithelial cells in all IPF cases with a mean value of 24.9% while it was seen in only two control patients in up to 5% of metaplastic cells. In patients with IPF, SCCA correlated positively with extension of fibroblastic foci (r = 0.49, p = 0.02), expression of TGFβ (r = 0.78, p<0.0001) and with carbon monoxide transfer factor decline after 9 months of follow-up (r = 0.59, p = 0.01). In vitro experiments showed that incubation of cultured cells with SCCA induced TGFβ expression, with a peak at 24 h. Conclusion: Our findings provide for the first time a potential mechanism by which SCCA secreted from metaplastic epithelial cells may exert a profibrotic effect in IPF. SCCA could be an important biomarker in this incurable disease.

Herpes Virus Infection Is Associated with Vascular Remodeling and Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis

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.

Thoracic aorta endograft as an adjunct to resection of a locally invasive tumor: A new indication to endograft

Covered stent grafts are currently used for arterial aneurysm exclusion, aortic dissection, or peripheral occlusive disease. A new indication to endograft was applied to perform resection of the thoracic aorta for infiltration of an adjacent lung cancer into the vessel wall, avoiding a major vascular intervention for aortic graft interposition associated with tumor resection.